Aging & Longevity
Integrin-Binding Matricellular Protein Fibulin-5 Maintains Epidermal Stem Cell Heterogeneity During Skin Aging
The extracellular matrix (ECM) is crucial in building the extracellular environment and translating extracellular information into biochemical signals that sustain tissue functions. Fibulin-5 (Fbln5) is a multifunctional ECM protein essential for forming elastic fibers and regulating cellular functions by binding to integrins. Although fibulin-5 expression decreases with age in human skin, its functional implications, particularly in epidermal stem cell regulation, remain largely unexplored....
Salidroside ameliorates skin aging in male mice by promoting collagen regeneration via modulation of FOS and MMP9
Salidroside, a phenolic compound derived from Rhodiola rosea L., has been widely utilized in cosmetics and medicine for its anti-melanogenic properties. However, its role in collagen regeneration during skin aging remains unclear. In this study, we investigated the effects of salidroside on collagen synthesis and explored its underlying mechanisms in a murine model of skin aging. Administering salidroside (20, 40, and 80 mg/kg) orally for 28 days significantly increased dermal thickness,...
Polysaccharide-Rich Herbal Formula Attenuates Skin Aging and Oxidative Stress in VCD-Induced Menopause Models via Regulation of AQP-3, C1QBP, and K19
To investigate the protective effects of Nvshi Oral Liquid on skin aging and oxidative stress in 4-vinylcyclohexene diepoxide (VCD)-induced menopausal rats and Ultraviolet B (UVB)-irradiated HaCaT cells. VCD-induced menopausal rats and UVB-damaged HaCaT cells under low-estrogen conditions were established. Nvshi Oral Liquid was administered at low (2%), medium (6%), and high (10%) concentrations. Cell viability, Reactive Oxygen Species (ROS) levels, antioxidant enzymes (superoxide dismutase...
Operationalizing a Decision-Making for Adverse Event Reporting Toolkit (DART) for Aging and Serious Illness Research
CONCLUSIONS: DART provides a novel solution to AE reporting challenges faced by aging and serious illness researchers. While its design centers on seriously ill older adults, DART can likely be applied to research in any population and intervention type not regulated by the FDA. Future pilot testing will inform implementation.
Validation and Evaluation of the Chinese Version of the Healthy Aging Questionnaire in Hong Kong
BACKGROUND: Healthy aging is a key public health priority in Hong Kong. The Healthy Aging Questionnaire, originally developed and validated in Singapore for older adults, is a concise tool for assessing multiple dimensions of healthy aging.
Mortality of People With Alzheimer's Disease and Psychiatric Morbidity: A Nationwide Finnish Cohort Study
CONCLUSION: Psychiatric comorbidity is associated with earlier AD onset and reduced lifespan; however, post-diagnosis survival appears to be largely determined by AD progression itself.
The rhythm of aging: Stability and drift in the individual rate of senescence
Human aging is marked by a steady rise in the risk of dying with age-a process demographers call senescence. Over the past century, life expectancy has risen dramatically, but is this because we are aging slower, or simply starting it later? Vaupel hypothesizes that the pace at which individuals age may be constant, with gains in longevity coming from the delayed onset of senescence rather than its slowing down. We test this idea using a framework that decomposes the pace of senescence into...
Luminal surface proteome of the brain vasculature uncovers blood-brain barrier regulators
At the blood-tissue interface, vasculature luminal surface is critical for molecular transport, signaling transduction, and cell extravasation. Here, we present a method for proteomic profiling of the vasculature luminal surface in vivo, broadly applicable to any vertebrate. Quantitative mass spectrometry revealed the luminal surface proteome of the mouse brain vasculature and its temporal evolution from development to aging. In vivo genetic perturbation found that the arginine transporter...
Genetic predisposition to hand grip strength predicts cognitive decline
Hand grip strength (HGS) is a predictor of cognitive decline in aging. To understand the direct and indirect mechanisms underlying this association, we performed integrative analyses of genetic, cognitive, and autopsy data. A polygenic risk score for HGS (PRS(HGS)) was calculated in two independent studies of aging (total n = 25,227). Cross-sectional and longitudinal modeling, including mediation with physical activity, assessed the effects of PRS(HGS) on cognitive performance and postmortem...
Age-related differences in memory encoding as a function of pupillary dynamics
Pupillary dynamics are known to depend on tonic and phasic activity of the brainstem locus coeruleus (LC), a key neuromodulatory nucleus. The LC shows a decline in its structural integrity in older age that likely impacts long-term memory. While several studies have explored the link between pupil dilation and successful memory encoding, little is known about the effects of aging on this relationship. This study investigated pupil dynamics in young and older adults during a rapid categorization...
Psychological Research on Alzheimer's Disease in Pakistan: A Systematic Review of Current Trends and Research Gaps
Alzheimer's disease (AD) is an escalating public health concern in low- and middle-income countries like Pakistan, with rising prevalence among the aging population. While global research has increasingly addressed the psychological dimensions of AD, Pakistan's contribution remains limited. This systematic review, conducted in accordance with PRISMA guidelines, examines the scope and focus of psychological research on AD in Pakistan. Eleven empirical studies published between 2014 and 2025 were...
Mitochondria-associated endoplasmic reticulum membranes as aging-sensitive signaling hubs in degenerative musculoskeletal diseases
Degenerative musculoskeletal diseases (DMDs), including osteoarthritis, osteoporosis, sarcopenia, and intervertebral disc degeneration, are highly prevalent age-related conditions characterized by progressive tissue dysfunction and loss of musculoskeletal integrity. Aging is accompanied by profound alterations in organelle homeostasis, metabolic signaling, and stress adaptation, among which mitochondria-endoplasmic reticulum communication has emerged as a critical regulatory axis....
The Role and Therapeutic Potential of DNA Glycosylases in Alzheimer's Disease
The aging brain is highly vulnerable to oxidative genomic damage, the accumulation of which is a hallmark of Alzheimer's disease (AD). The base excision repair (BER) pathway, initiated by DNA glycosylases, serves as the primary guardian against such damage. This review synthesizes recent evidence revealing the dual and dynamic roles of key DNA glycosylases including OGG1, MUTYH, MPG, and members of the NEIL family in AD pathogenesis. Beyond canonical repair functions, these enzymes actively...
Physical Function, Life Expectancy, and Cognitive Impairment in Older Adults: A 12-Year Longitudinal Cohort Study
CONCLUSIONS AND IMPLICATIONS: Maintaining good physical function in older adults is associated with increased life expectancy free of MCI or dementia, and may extend life without dementia in persons with MCI. These findings underscore the importance of promoting active aging to mitigate the burden of cognitive decline.
DUSP5 suppresses esophageal squamous cell carcinoma by counteracting macrophage-derived AREG-ERK1/2 signaling and disrupting an oncogenic ERK1/2-ELK1-DUSP5 feedback circuitry
Dual-specificity phosphatase 5 (DUSP5) is a key regulator of the mitogen-activated protein kinase (MAPK) pathway, with established roles in various types of cancer. However, its function in esophageal squamous cell carcinoma (ESCC) remains unclear. This study combines single-cell transcriptomics with in vitro and in vivo models to investigate the role of DUSP5 in ESCC. Single-cell RNA sequencing revealed tumor-infiltrating myeloid populations, including apolipoprotein C-positive (APOC⁺)...
Human cGAS Drives LINE-1 Transcriptional Activation to Trigger MAVS-Dependent Cellular Senescence
Long interspersed nuclear element 1 (LINE-1 or L1) retrotransposons pose a significant threat to somatic genomic integrity and are a source of sterile inflammation. Consequently, L1 activity is stringently controlled by multiple regulatory layers to ensure silencing, while its transcriptional derepression is linked to aging and age-related diseases. Recent studies have revealed complex interrelationships between L1 and cGAS, but whether cGAS regulates L1 transcription and its biological...
Single-Cell Profiling Reveals RAB13<sup>+</sup> Endothelial Cells and Profibrotic Mesenchymal Cells in Aged Human Bone Marrow
The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular changes associated with aging in humans remain poorly understood. Using single-cell RNA sequencing, we uncovered transcriptional shifts in BM endothelial cells (EC) and mesenchymal stromal cells (MSC) during aging. Aged sinusoidal EC exhibited a prothrombotic phenotype with compromised mitochondrial and vascular function. Additionally, we identified a novel arterial EC subset, emerging in...
Metformin promotes healthspan by attenuating frailty and preserving musculoskeletal function-structure in middle-aged mice
As global life expectancy rises, age-related musculoskeletal decline poses a growing public health challenge-impairing mobility, increasing frailty, and diminishing quality of life for billions worldwide. Functional deterioration often begins in midlife, yet effective early interventions remain limited. Metformin, a widely prescribed antidiabetic drug, has shown geroprotective potential. However, its capacity to preserve musculoskeletal health during early aging remains poorly defined....
Natural longevity modulator: aging modulatory effects of Eurycoma longifolia Jack polysaccharides in C. elegans and D. melanogaster
With the global rise in aging populations and age-related diseases, the demand for safe and effective aging modulatory interventions is steadily increasing. Although several clinical drugs have shown aging modulatory potential, their long-term efficacy and safety remain major concerns. Plant-derived polysaccharides, known for their ability to modulate multiple longevity-related signaling pathways, have emerged as promising natural candidates due to their high biocompatibility and low toxicity....
The influence of age and captivity on cardiac structure and function in rhesus macaques
Captive non-human primates are widely used as models of aging, yet the conditions they live in differ markedly from their natural environment. Such environmental differences may influence how the cardiovascular system changes with age. This study characterized age-related cardiac phenotypes in free-ranging rhesus macaques and compared these patterns to captive-housed macaques to assess the influence of environment on cardiac structure and function across the lifespan. We performed transthoracic...
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