Aging & Longevity

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...

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...

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...

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...

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...

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 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...

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.

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⁺)...

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...

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...

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....

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....

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...

Normal aging is accompanied by declines in executive function, and regular physical exercise has been proposed as a protective factor. However, the neural correlates linking long-term habitual exercise to executive efficiency in older adults remain unclear. This study combined resting-state functional magnetic resonance imaging (rs-fMRI) with behavioral assessments to examine whether long-term habitual exercise is associated with executive performance and resting-state neural organization in...

CONCLUSIONS: PCPs reported that they would often initiate opioid deprescribing conversations with older adults, but were less confident in managing older adults with signs of OUD. PCPs require additional support to implement successful conversations on opioid deprescribing with older adults.

We previously demonstrated that flattening circadian glucocorticoid (GC) rhythmicity without increasing overall GC exposure induces an osteoporotic phenotype in mice. Here, we aimed to further elucidate the importance of the amplitude and timing of circadian GC oscillations for bone health. C57Bl/6J mice were implanted with vehicle or corticosterone slow-releasing pellets to flatten the circadian GC rhythm. To differentiate between the importance of circadian GC peaks or troughs, mice with...

Handwriting is a complex cognitive and motor skill supported by a distributed brain network involving cortical, subcortical, and cerebellar regions responsible for planning, execution, and sensorimotor integration. Beyond its communicative role, handwriting provides biologically meaningful information about brain function and motor control, serving as a sensitive marker of both normal and pathological changes. Age-related alterations, such as reduced fine motor precision, impaired sensory...

Noise exposure is a known cause of hearing loss, and only a few effective preventive drugs are available. Therefore, in this study, we aimed to investigate the protective effects of brimonidine on noise-induced inner ear hearing impairment in mice and explore its underlying mechanisms and long-term outcomes. Mice were randomly divided into control, noise exposure, and brimonidine groups. A 62-week follow-up was conducted after noise exposure. Brimonidine inhibited the noise-induced increase in...

Aging has long been associated with oxidative stress, yet its underlying metabolic drivers remain unclear. Liu et al. identify a conserved, iron-driven lipid peroxidation of primate aging mediated by ACSL4 and demonstrate that vitamin C directly suppresses this process, offering a translatable strategy to mitigate age-associated functional decline.