Aging & Longevity

Ageing is a fundamental biological process marked by declining physiological function and the accumulation of stress-induced damage. It contributes to chronic disease and drives widespread alterations across organ systems, including the vasculature. Ageing of the macro- and microvasculature impairs nutrient delivery, promotes tissue degeneration, and reduces repair capacity in many tissues, including those of the musculoskeletal system. Tendons and ligaments become increasingly injury-prone with...

Aging is associated with blood-brain barrier (BBB) breakdown and microvascular rarefaction, key contributors to cerebral neuroinflammation, hypoperfusion, and vascular cognitive impairment and dementia (VCID). Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore BBB integrity and enhance cerebrovascular function in aged mice, suggesting that circulating factors can rejuvenate the aging brain. However, the molecular mediators responsible for these effects...

While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. Our previous work has shown that targeting aging pathways can be neuroprotective in animal models of neurodegenerative disease. Based on these findings, we believe that by gaining insight into the aging process that knowledge can be applied to identify novel therapeutic targets for neurodegenerative disease. To advance our understanding of aging, we...

CONCLUSION: Improvements in neuropsychological status and subjective memory were associated with reduced resting MCAv following exercise training. These exploratory associations suggest that variability in cerebrovascular responses may relate to cognitive responses; however, without consistent group-level effects, findings should be interpreted cautiously and do not imply causality.

INTRODUCTION: Hippocampal atrophy is frequently observed in neurodegenerative diseases such as Alzheimer's disease (AD) or hippocampal sclerosis of aging (HS-aging). Volume loss in the hippocampus is described as prodromal stage of dementia and has been associated with AD polygenic risk score (PRS). CA1 and subiculum atrophy have been suggested to be a promising in vivo biomarker for HS-aging. Recent studies suggest that some loci associated with AD may be more related to other brain diseases...

Cognitive decline and neurodegenerative diseases are progressive, multifactorial conditions that may begin years before overt clinical diagnosis and reflect interactions among biological vulnerability, modifiable exposures, environmental determinants, and reduced brain resilience. This structured narrative review examines how artificial intelligence (AI) and machine learning (ML) can integrate clinical, biological, behavioral, and digital data to support earlier, personalized, and clinically...

Aging is characterized by persistent low-grade inflammation linked to impaired tissue homeostasis, yet the underlying molecular mechanisms remain poorly understood. The mammalian skin is a clinically relevant site of aging-driven inflammation associated with compromised barrier function, inefficient wound healing, elevated oxidative stress and DNA damage accumulation. Here we show that, in the murine epidermis, aging engages a previously uncharacterized BMAL1-YAP functional cooperation with...

The human brain develops and matures over an exceptionally prolonged period of time that spans nearly two decades of life. Processes that govern species-specific aspects of human postnatal brain development are difficult to study in animal models¹. While human brain organoids offer a promising in vitro model, they have thus far been shown to largely mimic early stages of brain development. Here we develop human brain organoids for 5 years in culture, optimizing growth conditions to extend...

The detrimental impacts of cumulative obesity exposures and their interactions with genetics on biological aging remain poorly understood. We included 687 older adults (median age: 79.6 years) from the Rugao Longitudinal Ageing Study (RLAS), a community-based cohort study conducted in Rugao, Jiangsu, China. The cumulative exposures of body mass index (cBMI) and waist circumference (cWC) were calculated as the excessive exposure of BMI and WC relative to their reference values (BMI ≥ 24 kg/m²; WC...

CONCLUSIONS: The findings suggest that digital interventions tailored to the sociocultural needs of older adults may play an important role in promoting healthy aging and supporting mental well-being in India. Stakeholder-informed digital modules addressing physical health, sleep, emotional well-being, social connectedness, and self-care practices may enhance engagement, accessibility, and preventive mental healthcare among older adults. Future research should evaluate the effectiveness,...

Bone marrow stromal cells, marked by leptin receptor (Lepr) and C-X-C motif chemokine ligand 12 (Cxcl12), orchestrate osteogenesis and maintain bone homeostasis. Following injury, these stromal cells directly generate reparative bone and subsequently restore the marrow microenvironment, a process widely regarded as a reliable regenerative response. However, it remains unclear whether stromal cells retain full regenerative capacity after prior injury. Here, we show that Lepr^(+)Cxcl12^(+) stromal...

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Our previous study identified CD4 cytotoxic T lymphocytes (CD4 CTLs) as a hallmark of supercentenarians. CD4 CTLs have primarily been studied in disease contexts; however, their role in healthy aging remains unclear. Using single-cell immune profiling, we analyzed T cells from supercentenarians and found that CD4 CTLs begin to expand around the age of 100, characterized by sequential CD27/CD28 loss without exhaustion. CD4 CTLs were dominated by large clones, with top clones averaging 33.3%,...

Air pollution is the leading environmental cause of disease burden worldwide and is increasingly recognized as a potent driver of accelerated biological aging. Rather than acting through organ-specific toxicity alone, air pollutants appear to affect the fundamental hallmarks of aging itself, including oxidative stress, chronic inflammation, epigenetic dysregulation, telomere attrition, mitochondrial dysfunction, and cellular senescence. The pollutants of greatest concern are fine and ultrafine...

Aging features two linked immune traits: immunosenescence and chronic low-grade inflammaging. Other than senescent lymphocytes, pathologically remodelled macrophages are key drivers of age-related immune dysfunction, mainly via tryptophan (Trp) metabolism through the kynurenine pathway (KP) and microbiota-related indole pathway. This review suggests a bidirectional amplification loop model, in which dysbiosis of the microbiota in the aged gut causes decreased production of microbial indoles and...

Regulatory T (T(reg)) cells prevent autoimmune diseases but limit antitumor immunity. Tumor‑infiltrating Treg (Ti‑T(reg)) cells exhibit metabolic traits as potential antitumor targets. Here, we find that Ti-T(reg) cells upregulate glutamate dehydrogenase 1 (GDH1), increasing α-ketoglutarate (α-KG) levels. Elevated GDH1 in Ti-T(reg) cells accelerates tumor progression. Mechanistically, in a lactate rich microenvironment, GDH1 lactylation boosts α-KG production to fuel ALKBH5-mediated Wnt2...

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CONCLUSIONS: In our sample of studies evaluating CKD palliative care interventions, limited quality domains were addressed, a variety of measurement tools were used, and less than a quarter of studies were conducted only in older adults. Future research should address the holistic nature of palliative care, apply standardized instruments, and increase inclusion of older adults.

CONCLUSIONS: These findings highlight the adverse association of central adiposity and the limitations of BMI-only classification for mortality risk stratification in older adults.