Skin aging is one of the most common problems facing humanity. It occurs because of altering the balance between free radicals and antioxidants and increasing the amount of the reactive oxygen species (ROS) in skin cells, which leads to oxidative stress especially when exposed to UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites can help protect against UV radiation. In this study, punicalagin was extracted from pomegranate and concentrations of total polyphenolics and flavonoids were determined and antioxidant activities measured. Punicalagin was loaded onto niosomes and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin's effect. Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered of MMP3. Punicalagin increased human TERT concentration in skin cells. Punicalagin is promising as a natural antioxidant to protect human skin from aging.

Lifestyle health has been recognized as an evidence-based innovation that defines how daily habits and practices impact both the prevention and treatment of disease and provides an important adjunctive component to overall health. Specifically, an approach with small changes over time can have a dramatic impact on the health and well-being of individuals not only, in general, but also can be applied to skin health. However, lifestyle health factors to improve skin well-being have not been discussed extensively and/or well promulgated. The narrative for this overview focuses on providing a summary for topic background information, but more importantly, presents four lifestyle factors that can improve dermal health [i.e., factor 1: nutrition - diet; factor 2: rest (sleep); factor 3: movement/physical exercise, and factor 4: social and community associations]. This was accomplished by identifying previous journal articles and reviews with emphasis over the last five years (from January 2018 through July 2023; 156 out of 190 references cited or 82 %) using scientific search databases. The main conclusions of this overview encourage the concept that lifestyle health factors such as nutrition/diet, rest/sleep, movement/physical exercise, and community/social interactions support enhanced skin health and well-being with aging. Plus, social media interventions that aim to promote dietary, sleep and physical activity changes might be an application to improve skin health in the future.

Although relatively rare, affecting 8% of the general population, autoimmune disorders are causative linked with chronic diseases and morbidity. Control of the course of the disease is closely dependent on the ability to monitor its onset as well as response to treatment. In the present report, we review the progress in the development of biosensor-based approaches and related tools for the Point-of-Care diagnosis and monitoring of biomarkers related to several autoimmune diseases, such as Myasthenia Gravis, Rheumatoid Arthritis, Multiple Sclerosis, Systemic Erythematosus Lupus, Crohn’s Disease, Diabetes Mellitus, Behcet’s disease, Psoriasis and Celiac Disease. Various biosensing technologies are discussed, including electrochemical, optical and mechanical ones, along with the use of advanced nanomaterials and immobilization techniques for the biorecognition elements. The need for innovative devices with unique features of rapid, low-cost, real-time detection is considered in the context of preventing permanent organ and tissue damage from chronic autoimmune diseases.

Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

Aging causes various degenerative diseases in the older adult population. Senescence, a state of permanent cell-cycle arrest accompanied by the production of various pro-inflammatory factors known as senescence-associated secretory phenotype (SASP), is considered a significant contributor to the aging process and its chronic diseases. Ample evidence showed that various stressors could induce senescence, including DNA damage, telomere shortening and damage, activation of oncogenes, and mitochondrial dysfunction. Numerous credible findings indicate that environmental agents can induce senescence, including UV radiation, a high-fat diet, heavy metal exposure, and cigarette smoke. These findings posed the possibility that many more environmental agents may induce senescence and accelerate aging but remain unidentified. Senescence also becomes more intriguing due to its promising future as a pharmacological target to blunt the detrimental effects of aging and prevent aging-related diseases, either by eliminating the senescent cells or by controlling the SASP. On the other hand, investigating senescence has become more intricate due to the need for a multi-marker approach and translation in vivo analysis. This review will discuss senescence and its biomarkers, how to identify gerontogens in vivo, and also the development of senotherapy that targets senescent cells.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

Biomaterials play an important role in the development of advancing three dimensional (3D) in vitro skin models, providing valuable insights for drug testing and tissue-specific modeling. Commercial materials, such as collagen, fibrin or alginate, have been widely used in skin modelling. However, they do not adequately represent the molecular complexity of skin components. On this regard, the development of novel biomaterials that represent the complexity of tissues are becoming more important in the design of advanced models. In this study, we have obtained aged human decellularized dermal extracellular matrix (dECM) hydrogels extracted from cadaveric human skin and demonstrated their potential as scaffold for advanced skin models. These dECM hydrogels effectively reproduce the complex fibrillar structure of other common scaffolds, exhibiting similar mechanical properties, while preserving the molecular composition of the native dermis. It is worth noting that fibroblasts embedded within human dECM hydrogels exhibit behavior more representative of natural skin compared to commercial collagen hydrogels, where uncontrolled cell proliferation leads to material shrinkage. The described human dECM hydrogel is able to be used as scaffold for dermal fibroblasts in a skin aging on chip model. These results demonstrate that dECM hydrogels preserve essential components of the native human dermis making them a suitable option for the development of 3D skin aging models that accurately represent the cellular microenvironment, improving existing in vitro skin models and allowing for more reliable results in dermatopathological studies.

As global life expectancy continues to rise, we are challenged with maintaining health into old age, and research has thus concentrated on various strategies aimed at mitigating the effects of skin aging. Aromatic plants stand out as potential sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EO). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with Etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1β protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence associated β-galactosidase and p21/p53 protein levels and nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca²⁺ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway–regulated ERK1/2 and inositol trisphosphate (IP₃) signaling in NHDFs.

We conducted a research study to create groundwork for personalized solutions within skin aging segment. This test utilises genetic and general laboratory data to predict individual susceptibility of weak skin characteristics, leveraging on the research on genetic polymorphisms related to skin functional properties. A cross-sectional study was conducted in collaboration between the Private Clinic Medicina Practica Laboratory (Vilnius, Lithuania) and the Public Institution Lithuanian University of Health Sciences (Kaunas, Lithuania). 370 participants agreed to participate in the project. The median age of respondents was 40, with a range of 19 to 74 years. After the literature search, we selected 15 polymorphisms of the genes related to skin aging subsequently distributed for different skin functions: SOD2(rs4880), GPX1(rs1050450), NQO1(rs1800566), CAT (rs1001179), TYR (rs1126809), SLC45A2 (rs26722), SLC45A2 (rs16891982), MMP1(rs1799750), ELN (rs7787362), COL1A1(rs1800012), AHR (rs2066853), IL6 (rs1800795), IL1Beta (rs1143634), TNF-α (rs1800629), AQP3(rs17553719). RT genotyping, blood count and immunochemistry results have been analysed using statistical methods. Obtained results showed significant associations among genotyping models and routine blood screens. These findings demonstrate the personalized medicine approach for aging segment and further add onto the growing field of literature. Further investigation is warranted to fully understand the complex interplay between genetic factors, environmental influences, and skin aging.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

With the development of organizational biology and forced from the EU Cosmetic Regulation (EU/1223/2009) with the complete ban of animal testing for cosmetic purposes, 3D skin models have been widely developed due to their similar physiological structure and metabolic function to native human tissue. 3D skin models for in vitro cosmetic evaluation are still promising alternative methods for evaluating phototoxicity, corrosivity and irritation. These models have been used for early screening and later validation of toxicity and efficacy evaluation by many well-known cosmetic companies. 3D skin models have become an important tool in cosmetic evaluation research. This article reviews the development of 3D skin models and their application in cosmetic evaluation. An outlook on the current application and future technological development directions in the cosmetic field is also presented.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Skin photoaging is caused by prolonged exposure to ultraviolet (UV) radiation from sunlight. UV-exposed skin appears rough, thick, dry, loose, and shows deep wrinkles, and thickening. Our previous research showed that a Phaseolus angularis seed extract (PASE) effectively inhibits photoaging through UVB protection in HaCaT cells. However, its efficacy has not been evaluated in clinical trials so far. In this single-centered, randomized, double-blind study, we investigated the anti-aging effect of PASE in eye wrinkle areas. To these 21 healthy adult women aged 30 to 65, a PASE cream was applied to the right eye wrinkle area and a placebo to the left eye wrinkle area twice a day (morning and evening) for 12 weeks. The change in thick, deep crease wrinkles around the eyes was confirmed by visual evaluation, skin measurements, and a questionnaire. As a result, the R1 (surface roughness), R2 (maximum roughness), R3 (average roughness), R4 (smoothness depth), and R5 (arithmetic mean roughness) values in the group using the PASE cream all decreased. Particularly, R1, R4, and R5 significantly decreased by 18.1%, 18.6%, and 25.0%. In addition, no participants reported side effects. Our study showed that PASE led to clinically significant levels of wrinkle improvement. In conclusion, as PASE is a natural food, safe, and with few side effects, it can be a good resource for natural anti-wrinkle cosmetics in the future.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

This study introduces SkinLiTE, a lightweight supervised contrastive learning model, tailored to enhance the detection and typification of skin lesions in dermoscopic images. The core of SkinLiTE lies in its unique integration of supervised and contrastive learning approaches, which leverages labeled data to learn generalizable representations. This approach is particularly adept at handling the complexities and imbalances inherent in skin lesions datasets. The methodology encompasses a two-phase learning process. In the first phase, SkinLiTE utilizes an encoder network and a projection head to transform and project dermoscopic images into a feature space where contrastive loss is applied, focusing on minimizing intra-class variations while maximizing inter-class differences. The second phase freezes the encoder's weights, leveraging the learned representations for classification through a series of dense and dropout layers. The model was evaluated using three datasets from Skin Cancer ISIC 2019-2020, covering a wide range of skin conditions. SkinLiTE demonstrated superior performance across various metrics—accuracy, AUC , and F1 score—particularly when compared with traditional supervised learning models. Notably, SkinLiTE achieved an accuracy of 0.9087 using AugMix augmentation for binary classification of skin lesions. It also showed comparable results with the state-of-the-art approaches of ISIC challenge without relying on external data, underscoring its efficacy and efficiency. The results highlight the potential of SkinLiTE as a significant step forward in the field of dermatological AI, offering a robust, efficient, and accurate tool for skin lesion detection and classification. Its lightweight architecture and ability to handle imbalanced datasets make it particularly suited for integration into Internet of Medical Things environments, paving the way for enhanced remote patient monitoring and diagnostic capabilities. This research contributes to the evolving landscape of AI in healthcare, demonstrating the impact of innovative learning methodologies in medical image analysis.

Microwave radiation diagnosis technology can detect thermal changes in skin tissue earlier than anatomical changes, but its detection accuracy is limited by non-target radiation interference in the measurement environment, additional measurement errors of system units, and energy scattering and transmission between skin tissues. This paper aims to address the scientific challenges of analyzing the forward and inversion modelling detection mechanism of layered accurate temperature measurement of human skin tissue based on multi-band. The study focuses on the construction of a pencil beam antenna optimization system, the optimization strategy of high-sensitivity correlated radiometer architecture, and the high-precision multi-band forward and inversion modelling detection algorithm. The key technologies include: (1) A new method of integrated modeling and multi-index optimization of antenna with high directivity and small aperture is proposed, and a priori knowledge-guided neural network of pencil beam distribution is constructed to realize the inversion model of antenna structural parameters; (2) The influence mechanism of high sensitivity correlated radiometer architecture error is analyzed, and a periodic phase shift error correction algorithm based on uniform polar circle is designed; (3) Combining deep learning theory and hyperparameter optimization framework, an iterative model is established, and the objective function modified by the penalty factor is defined to realize a new detection method combining forward and inversion. This paper presents a theoretical foundation for the industrialization of microwave radiation diagnostic technology.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

The last decade has seen remarkable progress in the characterization of methylation clocks that track biological age in humans and many other mammalian species. While the biological processes of aging that underlie these clocks have remained unclear, several clues have pointed to a link to developmental mechanisms. These include the presence in the vicinity of clock CpG sites of genes that specify development, including those of the Hox (homeobox) and polycomb classes. Here we discuss how recent advances in programmatic theories of aging provide a framework within which methylation clocks can be understood as part of a developmental process of aging. This includes how such clocks evolve, how developmental mechanisms cause aging, and how they give rise to late-life disease. The combination of ideas from evolutionary biology, biogerontology and developmental biology open a path to a new discipline, that of developmental gerontology (devo-gero). Drawing on the properties of methylation clocks, we offer several new hypotheses that exemplify devo-gero thinking. We suggest that polycomb controls a trade-off between earlier developmental fidelity and later developmental plasticity. We also propose the existence of an evolutionarily-conserved developmental sequence spanning ontogenesis, adult development and aging, that both constrains and determines the evolution of aging.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

There is a skin allergy epidemic in the western world, and the rate of deterioration has increased significantly in the past 5-10 years. It is probable that there are many environmental contributing factors, yet some studies have linked it primarily to the rise in the use of synthetic chemical ingredients in modern cosmetics. Our challenge, therefore, was to find a mechanism to determine the effect these substances have on skin health, and whether they really are a primary cause of long term damage to the skin. The first problem is the lack of any definitive way to measure skin health. Motivated by the overwhelming evidence for a link between deficient gut flora and ill health, we decided to look at whether our skin microbiota could similarly be used as an indicator of skin health. Our research illustrates how it is microbiota diversity alone that can predict whether skin is healthy or not, after we revealed a complete lack of conclusive findings linking the presence or abundance of particular species of microbe to skin problems. This phenomenon is replicated throughout nature, where high biodiversity always leads to healthy ecosystems. ‘Caveman’ skin, untouched by modern civilisation, was far different to ‘western’ skin and displayed unprecedented levels of bacterial diversity. The less exposed communities were to western practices, the higher the skin diversity, which is clear evidence of an environmental factor in the developed world damaging skin. For the first time we propose benchmark values of diversity against which we can measure skin to determine how healthy it is. This gives us the ability to be able to predict which people are more likely to be prone to skin ailments, and start to test whether cosmetic ingredients and products are a main cause of the skin allergy epidemic.

Extracts of Cordyceps militaris which possess the bioactive capacity such as antimicrobial activity and DPPH-free radical scavenging capacity, are applied to the serum product. This finished serum product has been evaluated the in vitro bioactivity and the stability with expect to find out a good extract with a suitable percentage used for serum product as natural materials on preservatives and antioxidation.

The evolutionary theory of aging, particularly antagonistic pleiotropy (AP), provides an account of the ultimate origins of aging. What remains unclear is the nature of the proximate mechanisms by which AP gives rise to diseases of aging, like cardiovascular disease and Alzheimer’s disease. Damage-centric theories focusing on loss of genetic and cellular function have been proposed, as well as programmatic theories focusing on unwanted gene and cellular function. The latter include the hyperfunction and developmental theory that view aging as the futile continuation, or run-on, of growth and developmental programmes into later life. Yet neither type of theory has performed well in explaining late-life disease aetiology, particularly with respect to disease onset, presentation and progression. What is proposed here in this review is a new programmatic theory of aging. We argue that the emergence of many specific diseases may involve quasi-programmes that are not the result of run-on, but rather are triggered by other factors in late life. Such triggers may be non-programmatic (e.g. infection, mechanical injury) or programmatic. Moreover, the consequent pre-pathological and pathological changes may in some cases trigger further changes, leading to futile and destructive cascades of quasi-programmes and pathology. The origins of triggered quasi-programmes can be traced to biological constraint i.e. the inability of organisms to optimise all functions at once. And, to some extent, the new theory presented here revises the understanding of AP. That is, because any gene can be triggered in an erroneous manner, every gene is potentially an AP gene that risks pathology, though level of risk varies according to constraint. To help validate the theory, we test it against several complex diseases of aging. The new model in this review attempts to provide a blueprint understanding that, to a certain extent, closes the gap in the causal chain of events between evolutionary causes of aging and the aetiology of age-related diseases. It also helps to explain why certain disorders mimic accelerated aging and how interventions, such as the suppression of IIS and mTOR retard many aspects of aging; notably, though, unlike prior programmatic theories, the new theory is not mTOR-centric. Finally, it provides new perspectives on possible treatment of aging.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

In large-capacity energy storage systems, instructions are decomposed typically using an equalized power distribution strategy, where clusters/modules operate at the same power and durations. When dispatching shifts from stable single conditions to intricate coupled conditions, this distribution strategy inevitably results in increased inconsistency and hastened system aging. This paper presents a novel differentiated power distribution strategy comprising three control variables: the rotation status, the operating boundaries for both Depth of Discharge (DOD) and C-rates (C) within a control period. The proposed strategy integrates an aging cost prediction model developed to express the mapping relationship between these control variables and aging costs. Additionally, it incorporates the multi-colony particle swarm optimization (Mc-PSO) algorithm into the optimization model to minimize aging costs. The aging cost prediction model consists of three functions: predicting health features (HFs) based on the cumulative charge/discharge throughput quantity and operating boundaries, characterizing HFs as comprehensive scores, and calculating aging costs using both comprehensive scores and residual equipment value. Further, we elaborated on the engineering application process for the proposed control strategy. In the simulation scenarios, this strategy prolonged the service life by 14.62%, reduced the overall aging cost by 6.61%, and improved module consistency by 21.98%, compared with the traditional equalized distribution strategy. In summary, the proposed strategy proves effective in elongating service life, reducing overall aging costs, and increasing the benefit of energy storage systems in particular application scenarios.

Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and bio-logical processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. This narrative review article examines the existing literature on PBM, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of in-tracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on der-matology. Furthermore, advancements in PBM technology, such as novel light sources and treat-ment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.

Accumulation of damage is generally considered the cause of aging. Interventions that delay aging mobilize mechanisms that protect and repair cellular components. Consequently, research has been focused on studying the protective and homeostatic mechanisms within cells. However, in humans and other multicellular organisms, cells are surrounded by extracellular matrices (ECM), which are important for tissue structure, function and intercellular communication. During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

Abstract: Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. We identified several genes that appear to be involved both in natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved confirmed their possible roles in aging, suggesting the need for further in vitro and in vivo research. The graphical abstract illustrates the analysis workflow we used and will introduce in the following as an example to demonstrate the power of omics and bioinformatics.

This review summarizes current understanding of the interaction between circadian rhythms of gene expression and epigenetic clocks characterized by the specific profile of DNA methylation in CpG-islands which mirror the chronological age of individual cells and the entire organism. Basic mechanisms of regulation for circadian genes CLOCK- BMAL1 as well as downstream clock-controlled genes (ССG) are also discussed here. It has been shown that circadian rhythms operate by finely tuned regulation of transcription and rely on various epigenetic mechanisms including activation of enhancers / suppressors, acetylation / deacetylation of histones and other proteins as well as DNA methylation. Overall, up to 20% of all genes expressed by the cell are subject to expression oscillations associated with circadian rhythms. Also included in the review is a brief list of genes involved in the regulation of circadian rhythms, along with genes important for metabolic control, aging, and oncogenesis. Knocking out some of them (for example, Sirt1) accelerates the aging process, while overexpression of Sirt1, on the contrary, protects against age-related changes. Circadian regulators control a number of genes that activate the cell cycle (Wee1, c-Myc, p20, p21, and Cyclin D1) and regulate histone modification and DNA methylation. Approaches for determining the epigenetic age from methylation profiles across CpG islands in individual cells are described. DNA methylation, which characterizes the function of the epigenetic clock, appears to link together such key biological processes as regeneration and functioning of stem cells, aging and malignant transformation. Finally, main features of adult stem cell aging in stem cell niches and current possibilities for modulating the epigenetic clock as part of antiaging therapy are discussed.

For the past few decades, researchers have been intrigued with glassy polymers, which have applications ranging from gas separations to corrosion protection to drug delivery systems. The techniques employed to examine the sorption and diffusion of small molecules in glassy polymers are the subject of this review. Diffusion models in glassy polymers are regulated by Fickian and non-Fickian diffusion, with non-Fickian diffusion being more prevalent. The characteristics of glassy polymers are determined by sorption isotherms, and different models have been proposed in the literature to explain sorption in glassy polymers during the last few years. This review also includes the applications of glassy polymer. Despite having so many applications, current researchers still have difficulty in implementing coating challenges due to issues like as physical ageing, which is briefly discussed in the review.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.

The ability to predict the skin sensitization potential of small organic molecules is of high importance to the development and safe application of cosmetics, drugs and pesticides. One of the most widely accepted methods for predicting this hazard is the rodent local lymph node assay (LLNA). The goal of this work was to develop in silico models for the prediction of the skin sensitization potential of small molecules that go beyond the state of the art, with larger LLNA data sets and, most importantly, a robust and intuitive definition of the applicability domain, paired with additional indicators of the reliability of predictions. We explored a large variety of molecular descriptors and fingerprints in combination with random forest and support vector machine classifiers. The most suitable models were tested on holdout data, on which they yielded competitive performance (Matthews correlation coefficients up to 0.52; accuracies up to 0.76; areas under the receiver operating characteristic curves up to 0.83). The most favorable models are available via a public web service at https://nerdd.zbh.uni-hamburg.de/skinDoctor/ that, in addition to predictions, provides assessments of the applicability domain and indicators of the reliability of the individual predictions.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

The shortage of physicians in rural communities contributes to increased mortality rates among Medicare beneficiaries. This increase in mortality risk is commonly due to diseases such as heart disease and cancer, including melanoma and non-melanoma skin cancer (NMSC). Mohs micrographic surgery (MMS) is considered the gold-standard treatment for NMSC tumors, however, due to a shortage of dermatologists and Mohs surgeons in rural areas, access to MMS is limited. In these areas, image guided superficial radiation therapy (IGSRT) serves as a viable option for the treatment of NMSC lesions, with fewer recurrences and 99% cure rates, which are comparable to MMS cure rates. IGSRT is performed in dermatology clinics with support from a multidisciplinary team, including radiation therapists, medical physicists, radiation oncologists, and dermatologists. As IGSRT is able to be performed by general dermatologists, Medicare beneficiaries in rural communities will have an increase in access to treatment options and a decrease in delayed skin cancer treatment.

The leading cause of illness in aging is a group known as Noncommunicable Diseases. There should be some meeting points that modify the cells homeostasis and impaired the cell physiology developing different diseases. Quantum physics studied the atomic and subatomic particles and revolutionized the reality perception with paradoxical and weird concepts. Heisenberg's uncertainty principle established that it is not possible to determine the two characteristic properties of particles with accuracy. Subatomic particles have a wave-particle duality. Two subatomic particles are entangled, something happening over here can have an instantaneous effect over there, no matter how far away there are. All these concepts have tried to apply to biology and life sciences, quantum biology is behind photosynthesis, mitochondrial respiration, enzyme activity, the sense of smell, animal migration, heredity's fidelity, and consciousness. We can apply all these concepts to diseases pathogeny. So, we describe quantum phenomena in oxidative stress, calcification, signal transduction, vitamin D production and cancer mutations. Aging diseases also could be explained by applying quantum physics concepts. It is a new, hard to believe, and an incredible path to be built, but we need to open the treatment options to our patients with new perspectives.

Maintaining the high overall health of farmed animals is a central tenant of their well-being and care. Intense animal crowding in aquaculture promotes animal especially in the absence of straightforward methods for monitoring their health. Here, we used bacterial 16S ribosomal RNA gene sequencing to measure population dynamics occurring during P. salmonis outbreaks. Our findings revealed a complex bacterial community consisting of a previously undescribed core pathobiome. Notably, we detected Aliivibrio wodanis and Tenacibaculum dicentrarchi on the skin ulcers of salmon infected with P. salmonis, while Vibrio spp. were enriched on infected gills. The prevalence of these co-occurring networks indicates the influence that coinfection plays in P. salmonis pathogenicity.

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40-60μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have tremendous potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.

We investigate the impact of aging on exchangeable inter-arrival times in mixed renewal processes, exploring its implications for reliability and survival analysis. In this study, first, we revisit the definition of renewal point processes, where inter-event time intervals are considered as exchangeable non-negative random variables. Then, we define the concept of statistical aging as latency in the observational process of event counting. Latency affects event detection but preserves exchangeability. However, it may alter the statistical properties of inter-event time intervals. Our analytical and numerical assessments highlight the significance of aging in exchangeable lifetimes, offering insights into key metrics such as the failure survival function, renewal function, and hazard rate function. Through archetypal examples and empirical findings, we illustrate the implications of aging on renewal processes. In particular, employing a Bayesian perspective, we analyze high-frequency currency exchange rate data to assess the impact of aging on volatility risk evaluation. This study contributes novel insights to the literature of renewal theory and survival analysis, emphasizing the role of latency aging in stochastic point processes under exchangeability assumption.

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

Capacitive contact imaging has shown potential in measuring skin properties including hydration, micro relief analysis, as well as solvent penetration measurements. Through calibration we can also measure the absolute permittivity of the skin, and from absolute permittivity we then work out the absolute solvent content in skin. In this paper, we present our latest study of capacitive contact imaging for skin characterizations and vivo skin solvent penetration. We will show how to use capacitive occlusion measurements to characterize skin damages, and how to calculate the absolute water content and solvent content in skin.

Optical tissue imaging has several advantages over the routine clinical imaging methods, including non-invasiveness (does not change the structure of tissues), remote operation (avoids infection) and ability to quantify the tissue condition by means of specific image parameters. Dermatologists and other skin experts need compact (preferably pocket-size), self-sustained and easy-to-use imaging devices. The operational principles and designs of ten portable in-vivo skin imaging prototypes developed at the Biophotonics Laboratory of Institute of Atomic Physics and Spectroscopy, University of Latvia during the recent five years are presented in this paper. Four groups of imaging devices are considered. Multi-spectral imagers offer possibilities for distant mapping of specific skin parameters, so facilitating better diagnostics of skin malformations. Autofluorescence intensity and photobleaching rate imagers show a promising potential for skin tumor identification and margin delineation. Photoplethysmography video-imagers ensure remote detection of cutaneous blood pulsations and can provide real-time information on cardiovascular parameters and anesthesia efficiency. Multimodal skin imagers perform several of the above-mentioned functions by taking a number of spectral and video images with the same image sensor. Design details of the developed prototypes and results of clinical tests illustrating their functionality are presented and discussed.

Senescence-accelerated mouse prone 8 (SAMP8) mice exhibit cognitive defects and neuron loss with aging, and are used to study anti-aging effects of Dendrobium nobile alkaloids (DNLA). SAMP8 mice were orally given DNLA from ages 6 to 10 months. At 10 months of age, behavioral tests and neuron damage were evaluated. Protein was extracted and subjected to phosphorylated proteomic analysis. The cognitive deficits and neuron loss in hippocampus and cortex of aged SAMP8 mice were improved by DNLA. Hippocampal proteomic analysis showed differentially expressed protein/genes in SAMP8 compared to age-matched senescence-accelerated resistant mice, including altered tubulin binding, microtubule binding, etc. via Gene Oncology. KEGG revealed endocytosis, mRNA surveillance, tight junction, protein processing in endoplasmic reticulum, aldosterone synthesis and secretion, and glucagon signaling pathway changes. Upregulated protein/genes in the hippocampus of SAMP8 mice, such as Lmtk3, Usp10, Dzip1, Csnk2b, and Rtn1, were attenuated by DNLA; whereas downregulated protein/genes, such as Kctd16, Psd3, Bsn, Atxn2l, and Kif1a, were rescued by DNLA. The aberrant protein/gene expressions of SAMP8 mice were correlated with transcriptome changes of Alzheimer’s disease in the GEO database, and were attenuated by DNLA. Thus, DNLA improved cognitive dysfunction and ameliorated neuronal injury in aged SAMP8 mice, and attenuated aberrant protein/gene expressions.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.

The study of the human microbiome has been a hot topic during the last decades and more recently the skin microbiome has aroused great interest as well. So that, scientists have turned their attention to the role of the skin microbiome in skin health, and its relationship with different disorders as atopic dermatitis, psoriasis, acne, and rosacea, among others. Numerous studies and investigations have been performed to study the role of pre and probiotics as nutraceuticals in the treatment of skin diseases, with growing evidence along the last ten years. This review gathers information on the use of “nutribiotics” in skin care health, focus on the main dermatological diseases and other skin conditions. Clinical studies show that nutribiotics could be a new tool to improve skin health and pre, pro, syn, post and para-probiotics seem to be beneficial on several skin disorders, as well as repairing the skin barrier, or promoting wound healing. In conclusion, skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Future advances in this field may facilitate the treatment of skin dysbiosis being nutribiotics a suitable method for skin care.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: describe briefly the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article, it must not contain results which are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Melatonin is a hormone used for treating several disorders. However, its oral administration is problematic due to the variable absorption and extensive first-pass metabolism. The topical application of this drug does not present these disadvantages and can be used for therapeutic and skin protection purposes. The adsorption and release of melatonin in the montmorillonite clay was investigated experimentally and theoretically. The drug-clay interaction products were prepared and characterized, showing a modified and improved diffusion and release of melatonin. The crystal structure and spectroscopic properties of melatonin and melatonin-water-mineral materials were studied by molecular modeling, finding that the adsorption of this drug is energetically favourable, and the results were consistent with the experimental data. Ab initio molecular dynamics simulations with the metadynamics methodology showed the release of melatonin from the confined interlayer nanospace of montmorillonite to the liquid bulk water with a 20 kcal/mol free energy barrier.

The metaphor of being touched by music is widespread and almost universal. The tactile experience, moreover, has received growing interest in recent years. There is, however, a need to go beyond a mere metaphorical use of the term, by positioning the tactile experience within the broader frame of embodied cognition and the experiential turn in cognitive science. This article explores the possible contribution of a science of touch by defining music as a vibrational art that impinges upon the body and the senses. It takes as a starting point the clinical findings on the psychological and physiological value of tender touch with a special focus on the method of kangaroo mother care, which is a method for holding the baby against the chest of the mother, skin-to-skin. It is seen as one of the most basic affiliative bonding with stimuli that elicit reward. Via an extensive review of the research literature, it is questioned to what extent this rationale can be translated to the realm of music. There are, in fact, many analogies, but a comprehensive theoretical framework is still lacking. This article aims at providing at least some preparatory groundwork to fuel more theorizing about listening and its relation to the sense of touch.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin may to some extent exacerbate every other kind of age-related damage. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss a method of removing it from single cells in vitro.

The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

We discuss the neutron skins of 48Ca and 208Pb. We review and critically examine modern predictions and empirical constraints, with special attention to the dierent interpretations of the ndings from the PREX-II experiment and the recently reported value of the neutron skin in 48Ca extracted from the CREX experiment. We argue that, in the spirit of the ab initio philosophy, the path to understanding the behavior of dense neutron-rich matter must not circumvent fundamental nuclear forces. Based only on that argument, a thick neutron skin in 208Pb is highly unlikely.

Keywords: Convolutional Neural Network, Deep Learning, Skin cancer, Generative Adversarial Network

Humans have extremely variable skin pigmentation and melanin production influenced by genetics, UV exposure, and some medications. A significant number of skin illnesses that result in pigmentary abnormalities have an impact on patients’ physical appearance as well as their psychological and social well-being. Skin pigmentation can be divided into two basic categories: hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced. Albinism, melasma, vitiligo, Addison's disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosine, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, four marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Tobacco smoke is an environmental mixture including polycyclic aromatic hydrocarbons and may interfere in endocrine system as an EDC in aging. Thus, we performed a molecular epidemiological approach with in-depth biological monitoring of combustible cigarette smoking among adolescents and adults in South Korea (N=620) with exposure biomarkers, i.e., exhaled CO, urinary cotinine, t,t-muconic acid (TTMA), malondialdehyde (MDA), and obtained information of their lifestyle and tobacco addiction status. We also diagnosed the genetic polymorphisms on the 96 SNPs for tobacco-metabolism, -addiction, and expression differences and compared mtDNA abnormalities in buccal and blood cells. As results, there were positive associations among the above tobacco exposure biomarkers. Man or youth smokers showed high frequency in some of mtDNA alteration, such as ‘SNPs for inconsistent bases between buccal and blood cells’. Among the SNPs, the polymorphisms on SULT1A1, DRD2, and ADH1B were related to multi-exposure biomarkers. Interestingly, youth showed similar levels of urinary TTMA and MDA to adults, although their pack-year was approx. 1/6 volume of that of adults. We also observed the negative association between urinary MDA levels and the growth rate in the adolescents (p<0.05). In conclusion, the present biological monitoring provides high susceptible population, i.e., adolescents rather than adults, and reliable genetic factors affecting tobacco exposure. The inferred environment-gene-gene interaction suggests tobacco smoking accelerats aging in adolescents as an EDC.

Abstract: Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but extant studies are limited in interval of assessment (2-5 years). We studied cognitive performance in a cohort of survivors and controls utilizing cross-sectional cognitive performance data from age 60 to 89 years as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5– to 15-year survivors (N=328) and non-cancer controls (N=158) were assessed at enrollment and at 8, 16 and 24 months with standard neuropsychological tests and comprehensive geriatric as-sessment. Results: Cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower than controls in learning and memory (LM) but not in attention, processing speed and executive function (APE). Younger survivors, i.e., those under 75 years of age, exhibited early decline in performance in both LM and APE compared to controls, with no differences between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Differences between survivors and controls were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging.

The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p &lt; 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.

Nanostructured carriers have been widely used in pharmaceutical formulations for dermatological treatment. They offer targeted drug delivery, sustained release, improved biostability, and low toxicity, usually presenting advantages over conventional formulations. Due to its large surface area, small size and photothermal properties, graphene oxide (GO) has the potential to be used for such applications. Nanographene oxide (GOn) presented average sizes of 197.6 ± 11.8 nm, and a surface charge of -39.4 ± 1.8 mV, being stable in water for over 6 months. 55.5 % of the mass of GOn dispersion (at a concentration of 1 mg mL-1) permeated the skin after 6 h of exposure. GOn dispersions have been shown to absorb near-infrared radiation, reaching temperatures up to 45.7 °C, within mild photothermal therapy temperature range. Furthermore, GOn in amounts superior to those which could permeate the skin were shown not to affect human skin fibroblasts (HFF-1) morphology or viability, after 24 h of incubation. Due to its large size, no skin permeation was observed for graphite particles in aqueous dispersions stabilized with Pluronic P-123 (Gt-P-123). Altogether, for the first time, GOn potential as a topic administration agent and for delivery of photothermal therapy has been demonstrated.

Photoacoustic imaging (PAI) is a cutting-edge biomedical imaging modality, providing detailed anatomical and functional information about the area beneath the skin surface. Its light energy deposition is such that PAI typically provides clear images of the skin with high signal-to-noise ratios. Specifically, the rich optical contrast of PAI allows biological information related to lesion growth, malignancy, treatment response, and prognosis to be seen. Given its significant advantages and emerging role in imaging skin lesions, we summarize and comment on representative studies of skin PAI, such as the guidance of skin cancer biopsies and surgical excisions, and the accurate diagnosis of psoriasis. We conclude with our insights about the clinical significance of skin PAI, showing how its use to identify biological characteristics in lesion microenvironments allows early diagnosis and prognosis of disease.

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the ex-pression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug, 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of ectoine in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA methyla-tion-related gene and marker analysis were performed. The results showed that ectoine hypo-methylation in skin cells, especially in the CpG island (CGIs) element and 5mC, was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation, but did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3i, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Igf2, Snrpn, and Mest. Overall, ectoine, an excellent DNA protectant, mildly de-methylates DNA in skin cells, modulates the expression of methylation-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.

This short communication reports on the initial results of a much larger, ongoing project, the aim of which is to investigate the question: could the skin microbiome, just like the gut microbiome, play a role in sports recovery and performance – and if so, could this role be as significant a one as that played by the gut microbiome? 17 high performance college athletes addressed their skin microbiome by minimizing contact with synthetic chemicals and by using topical skin supplements, shown previously to significantly increase skin microbiome biodiversity, for two weeks after training. 76% said their skin softness improved, 35% said their muscle stiffness and recovery after sport improved, 12% said their sleep quality improved, and 100% said they would be likely to use skin supplements again. Future work will use hundreds of athletes.

The circadian clock regulates daily changes in behavioral, endocrine and metabolic activities in mammals. Circadian rhythms in cellular physiology are significantly affected by aging. In particular, we previously found that aging has profound impact on daily rhythms in mitochondrial functions, leading to increased oxidative stress. However, this is unlikely due to malfunction of molecular clocks in the suprachiasmatic nucleus or peripheral tissues, as robust clock oscillations are observed therein in old animals. Nonetheless, aging induces changes in gene expression levels and rhythms in various peripheral and probably central tissues. In this article, we review findings on the roles of the circadian clock and aging in regulating mitochondrial rhythms and redox homeostasis. Chronic sterile inflammation is implicated in mitochondrial dysfunction and increased oxidative stress during aging. In particular, upregulation of CD38 by inflammatory response can disturb mitochondrial functions in multiple ways.

Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role, and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

The CuCrSn alloy is promising as high-strength and high-conductivity Cu alloy due to its relative low smelting requirement, while thus far reports on the CuCrSn alloy is still quite lacked. In this study, the microstructure and properties of Cu-0.20Cr-0.25Sn (wt%) specimens prepared under different rolling and aging combinations were comprehensively characterized, in order to reveal the effects of cold rolling and aging on the CuCrSn alloy. The results show that increasing the aging temperature from 400 ºC to 450 ºC can obviously accelerates the precipitation, and the cold rolling before aging significantly increases the initial microhardness and promotes the precipitation. Whereas, the deformation hardening will be eliminated during the aging process, making the microhardness even decrease monotonically when the aging temperature and the rolling ratio before aging are high. Performing the cold rolling after the aging can maximize the effects of precipitation strengthening and deformation strengthening, and its adverse impact on the conductivity is not serious. A tensile strength of 506.5 MPa and a conductivity of 70.33% IACS were obtained with such a treatment, only the elongation decreases. Different strength-conductivity combinations of the CuCrSn alloy can be achieved through appropriate combinations of the aging and post aging cold rolling conditions.

A face serum composed of a combination of biologically active compounds was evaluated for safety and efficacy in vitro, in a repeat insult patch test and in a human clinical efficacy trial. The serum inhibited tyrosinase activity modestly, decreased collagenase activity and exhibited notable free radical scavenging activity in vitro. It is gentle to the skin, as the serum did not irritate the skin or produce symptoms of allergic contact dermatitis in the 55 healthy adults that participated in the repeat insult patch test. In the efficacy trial, daily application of the face serum for 30 days significantly increased skin hydration, with all 35 volunteers experiencing improvement. Substantial improvements in skin elasticity, roughness (fine lines and wrinkles), and brightness also occurred during the trial. Dermatological examination also revealed a trend for reduced comedone count with use of the serum. Self-assessment responses revealed that all volunteers experienced improvements in multiple skin quality parameters and that participant perceptions are consistent with the results of the instrumental analyses. These findings indicated that the measured improvements in skin quality are not only statistically significant but are also clinically relevant as they were great enough for users of the face serum to feel and recognize.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

Post-ovulatory aging (POA) is an inevitable factor during some assisted reproduction technology procedures, and results in poor fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and in vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte(A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte(A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched GO terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. WGCNA analysis to explore gene expression modules specific to A_vivo. Trait-modules association analysis showed that the red modules were most associated with in vivo aging. There are a total of 959 genes in the red module, which are mainly enriched in “RNA binding”, “mRNA metabolic process”, etc. GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. And these genes were all expressed higher in A_vivo. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study helps us understand the detailed mechanism of POA and provides strategies for researching oocyte aging.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

Programmed aging refers to the idea that mammals (and some other multiparous sexually reproducing organisms) evolved complex biological mechanisms that cause gradually increasing fitness deterioration and internally limit individual organism lifetimes. The rationale is that this process enhances the survival (non-extinction) of a species population. Evolvability theories propose that mammals have evolved design characteristics that aid their ability to evolve, that is, reduce the time required for a particular increment of evolutionary adaptation and/or increase the precision with which the adaptation can be performed. Because an increase in evolvability aids a population in escaping extinction, evolution selects the associated design characteristics. Both of these concepts conflict with traditional (Darwinian) theory regarding the nature of evolution. However, more recent genetics discoveries have exposed rich detail regarding the nature of the evolution process including the fact that biological inheritance involves the transmission of organism design information from parent to descendant in digital form. These discoveries have acted to support both programmed aging and evolvability theories. Acquisition traits are those that depend for their evolutionary (fitness) value on the acquisition of something that gradually accumulates during an organism’s life but is not transmitted genetically to descendants. This situation causes these traits including language, immunity, intelligence, and social status to represent a special need for evolvability and programmed aging.

Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMs^Enz and PTMs ^Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (Rz^Sp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.

An accumulating body of evidence suggests that physiological reactive oxygen species (ROS) generated by NADPH oxidases act as a redox signal to re-establish homeostasis, a capacity that progressively declines during aging, but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox to generate ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: 1) enzymatic activity to catalyze cross-linking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, 2) high ROS bursts/levels to kill pathogens, and 3) Redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress- and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases and their relevance for human aging are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.

Knowing that biomolecules, such as β-amyrin and α-amyrin, have some pharmacological effects, the aim of this study was directed towards exploring the protective effect of a Tomato Peel and Seed Extract (TPSE) for its soothing function but also for its capacity to modulate the adrenal axis, involved in stress response. Ex vivo tests were carried out on skin explants to evaluate the effectiveness of TPSE formulated at 0.5% on Calcitonin Gene-Related Peptide (CGRP) and IL-10 release, Kappa Opioid Receptor (KOR) and Caspase 14 expression. An in vivo study combined a clinical evaluation of skin homogeneity, psychological parameter as well as analysis of salivary cortisol and dehydroepiandrosterone concentrations. All measurements were carried out at the beginning and after 28 days of applying a TPSE face cream. TPSE regulated not only the release of CGRP and Il-10, reflecting an anti-neurogenic and anti-inflammatory properties, but also modulated KORs. Twenty height days of TPSE application induced a significant decrease in intensity and extent erythrosis, a lower output of salivary cortisol and a significant increase in pleasant emotions when compared to placebo. These results provide encouragement to continue exploring the impact of cosmetic ingredient on psychophysiological parameters to improve skin health and well-being.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

In recent years, computer-aided analysis techniques have emerged as valuable tools in assisting dermatologists by providing objective and efficient analysis of skin cancer images. This paper utilizes the combination of the Contourlet Transform (CT) and Local Binary Pattern (LBP) techniques for accurately recognizing borders, contrast changes, and shapes of skin cancer images. These results often contain many features, leading to high computational costs and potential over-fitting issues. Hence, we applied Particle Swarm Optimization (PSO) to select the most informative and discriminating features, reducing the dimensionality while retaining important information for accurate classification. After reducing the feature set with PSO, we applied these sets to Machine learning classification algorithms: Support Vector Machine (SVM), Random Forest (RF), and Neural Networks (NN). The results show that SVM has the lowest time complexity of 0.0458 seconds, followed by the Neural Network at 0.08730 seconds, and the Random Forest model has the highest time complexity of 0.1622 seconds. The SVM and Neural Network models are faster to train than the Random Forest model, making them more suitable for real-time or latency-sensitive applications. We also compared our proposed model with the state-of-the-art models and obtained the accuracy of 86.9%, which is the highest among the models.