Aging & Longevity

The 9p21 locus encodes critical cell cycle regulators p16^(INK4A), p14^(ARF), and p15^(INK4B) and contains a high density of SNPs associated with aging-related diseases. Progress toward understanding 9p21 regulatory mechanisms has been constrained by complex transcript structures and a shortage of cell models that retain physiologic locus control. We innovated tools to deconvolve the expression and regulation of 9p21 transcripts in single cells. We find that 9p21 transcripts exhibit highly...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Familial AD accounts for less than 1% of cases, while sporadic AD (SAD) accounts for over 95%. Mild cognitive impairment (MCI) is the critical transition phase from normal aging to AD dementia. Understanding the pathological progression from MCI to AD and the mechanisms underlying SAD is essential. Rodent models, including transgenic and non-transgenic models, are vital tools for developing effective AD therapies. However,...

Sarcopenia and cognitive decline frequently co-occur in older adults, and growing evidence indicates that these conditions share a common biological substrate centred on the muscle-brain axis. In this narrative review we synthesise contemporary mechanistic and translational evidence on how skeletal muscle communicates with the ageing brain through myokines and exerkines - including irisin/FNDC5, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1),...

Aging is characterized by progressive physiological decline and accumulation of senescent cells that drive chronic "inflammaging" through the senescence-associated secretory phenotype (SASP). The complement system, traditionally viewed as a systemic extracellular defense mechanism, is now recognized as an essential intracellular network (the complosome). This review synthesizes current research on how intracellular C3 (intC3), and intracellular C5 (intC5) in certain contexts engage in extensive...

The human microbiome profoundly influences host physiology, metabolism, and immune function. A balanced microbial ecosystem supports immune homeostasis and health, whereas dysbiosis contributes to diverse diseases, including metabolic, autoimmune, neurodegenerative, and infectious disorders. Aging, the greatest risk factor for chronic disease, is characterized by hallmarks such as mitochondrial dysfunction, genomic instability, and "inflammaging," a state of chronic low-grade inflammation....

Healthy and pathological aging are associated with progressive changes in cortical inhibition, yet the underlying neural mechanisms remain incompletely understood. Somatosensory gating (SG), the brain's suppression of redundant tactile input, provides a pre-attentive marker of inhibitory function. Paired-pulse paradigms concurrent with noninvasive magnetoencephalography (MEG) provide a millisecond portrayal of the neural dynamics underlying somatosensory processing and the gating of such...

Inflammaging, the chronic subclinical systemic inflammation accompanying aging, represents a critical pathogenetic mechanism underlying age-related neurodegenerative diseases. While amyloid beta (Aβ) peptides are established contributors to neuroinflammation in Alzheimer's disease, their role in aging-related subclinical inflammation remains insufficiently elucidated. In humans, Aβ exhibits dual functions: it supports neuronal activity, survival, and protection against neurotrauma, while also...

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Nonhuman primates are widely used in preclinical biomedical research, with hematobiochemical values serving as key clinical pathology parameters for assessing health status. In this study, we collected and analyzed 2973 blood samples from 566 cynomolgus macaques and 193 rhesus macaques, along with anthropometric measurements such as BMI, body weight, and waist circumference. Corresponding human data were obtained from the NHANES database and incorporated into the study. Regarding white blood...

Although individual social determinants of health (SDoH) are known to influence non-alcoholic fatty liver disease (NAFLD) outcomes, the cumulative effect of comprehensive SDoH exposure and the underlying biological pathways remain largely unaddressed. We analyzed 3025 adults with NAFLD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycles. We utilized weighted Cox proportional hazards models to evaluate individual SDoH variables. To assess the joint effect of the...

Alzheimer's disease (AD) is the most common cause of dementia and major public-health challenge in aging societies worldwide. Accumulating evidence suggests that olfactory and visual deficits can precede overt cognitive symptoms and are closely associated with amyloid-β deposition, pathological tau phosphorylation, and disease progression. Early sensory abnormalities in AD likely arise from converging pathological processes. Among these, chronic neuroinflammation marked by microglial and...

Chronic stress in mice causes anxiety and hyperglycemia by inducing senescence in amygdala astrocytes.

Aging impairs intestinal stem cell (ISC) function, disrupting epithelial homeostasis and regenerative repair. Loss of ISC quiescence promotes intestinal dysfunction and contributes to organismal aging. Here, we report an epitranscriptomic mechanism through which a decrease in adenosine-to-inosine (A-to-I) RNA editing by the adenosine deaminase ADAR in ISCs during aging disrupts a conserved signaling axis that maintains ISC quiescence. In Drosophila melanogaster, ISC-specific loss of dADAR...

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review...

Endothelial senescence is a critical contributor to vascular aging and age-related vasculopathies. Our previous work identified AGGF1 as a regulator of cell cycle progression and anti-inflammatory signaling. However, whether AGGF1 modulates endothelial senescence remains unclear. Here, we demonstrate that AGGF1 is downregulated in both replicative and DOX-induced senescent HUVECs. AGGF1 knockdown accelerated cellular senescence as evidenced by senescence markers, including increased SA-β-gal...

Evidence on meal timing and dementia is limited. We examined late-night dinner and skipping breakfast in relation to incident dementia. We conducted a population-based cohort study using linked medical insurance claims, long-term care insurance claims, and government-subsidized health checkup data from 19 participating in the Longevity Improvement & Fair Evidence (LIFE) Study. Cohort entry was from April 2016 to March 2021. Late-night dinner (dinner within 2 h of bedtime ≥ 3 times/week) and...

PurposeTo identify the predictors of the technology-assisted behaviors older adults would consider implementing once encountered with a health concern and seeking help. To understand this phenomenon, the study tapped into the technology familiarity approach and the media richness theory.MethodsData were obtained from the 2020 wave of the Ageing, Communication, Technologies (ACT) survey and analyzed using logistic regression models. The sample included 3,926 internet users 63-97 years old from...

Age-related cognitive decline is increasingly recognised as arising from interacting immune and neurovascular vulnerabilities rather than from isolated insults. In this Review, we synthesise current human and mechanistic evidence within a convergence framework in which inflammaging and neurovascular unit (NVU) dysfunction are conceptualised as a feedback-coupled system. Persistent immune remodelling may promote endothelial activation, redox imbalance, pericyte-astrocyte support failure,...

CONCLUSIONS: The findings indicate that the cognitive effects of multi-session resistance exercise are domain-specific rather than uniform across cognitive abilities. Resistance exercise appears particularly promising for supporting cognitive processes involving executive control, working memory, and rapid information processing. However, interpretation should remain cautious given heterogeneity across studies, limited evidence in some domains, and variation in intervention duration, intensity,...