Aging & Longevity

Aging is associated with increased oxidative stress, which leads to pathological vulnerability. Spermidine is a ubiquitous natural polyamine found across all living organisms studied so far and present in multiple food sources. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentration and age-related organ degeneration has been proposed. We outline recent studies that address the potential contribution of spermidine to...

Microglia, the resident macrophages of the CNS parenchyma, are recognized as highly plastic, transcriptionally diverse cells whose phenotypes are moulded by development, region, sex, age, genotype and environment. Advances in single-cell and single-nucleus transcriptomics, chromatin accessibility profiling, and spatial multi-omics have negated binary frameworks of 'resting versus activated' or 'M1 (pro-inflammatory) versus M2 (anti-inflammatory)' and revealed a multidimensional state space that...

Cytoskeleton is an important component of cell structure and function. In the cardiovascular system, it is involved in the remodeling process of a variety of cardiovascular diseases, including cardiac fibrosis, valvular disease, atrial fibrillation, thoracic aortic aneurysm and vascular stiffness related changes. Recent studies have shown that there is a significant synergy between cytoskeletal regulation and epigenetic processes. Notably, epigenetic alterations have been identified as one of...

Aging is a biologically tractable process. Telomerase reverse transcriptase (TERT) has emerged as an upstream regulator coordinating several hallmarks of aging across preclinical models. Beyond maintaining telomeres, TERT influences mitochondrial health, epigenetic regulation, inflammation and stem cell function. Multiple translational strategies are being explored to modulate TERT. In mice and human cell models, restoration of physiological-range TERT expression characteristic of younger cells,...

Unsupervised serious video games on the SmartMe&You home telemonitoring platform may enable the assessment of cognitive fluctuations in older individuals, with or without cognitive deficits. Here, we tested their validity in cognitively unimpaired older adults (Healthy) and patients with mild cognitive impairment and mild to moderate dementia due to Parkinson's disease (PDCD). Such validity was assessed using Mini-Mental State Examination (MMSE) scores and resting-state eyes-closed...

Epigenetic clocks derived from DNA methylation robustly predict biological aging, health, and mortality, yet differ substantially in their predictive profiles. The biological processes underlying these differences remain poorly understood. Using data from 3227 participants in the U.S. Health and Retirement Study, with contemporaneous DNA methylation and RNA-sequencing, we examined the five most widely used epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE). We conducted...

CONCLUSIONS: Objectively measured sensory impairments were highly prevalent among US older adults and were associated with an increased risk of anxiety, but not depressive symptoms over a short follow-up duration. Self-reports considerably underestimated true prevalence of mild- to- moderate impairment, emphasizing the need for routine objective assessment in clinical practice and research.

CONCLUSIONS: The T-EAT-10 is a practical and highly effective screening tool for identifying aspiration pneumonia risk in institutionalized elderly populations. A clinical threshold of >12 is recommended for identifying high-risk residents, which is substantially higher than the standard dysphagia screening cut-off. Systematic screening using T-EAT-10 and NUFFE-TR should be integrated into routine geriatric care in nursing homes to improve preventive strategies.

Aging hematopoiesis exhibits progressive myeloid skewing and impaired lymphopoiesis, driving age-related blood disorders. We show that multipotent progenitors (MPPs) mediate this lineage imbalance. Aging expands myeloid-biased MPP3 cells while functionally compromising MPP4 lymphoid potential, collectively skewing hematopoietic output toward the myeloid lineage. We identify Bcl11a as a dosage-sensitive regulator of MPP fate: Bcl11a suppresses Fer to restrain premature myeloid differentiation in...

CONCLUSION: Public health strategies should emphasize physical activity, healthy diets, weight control, and improved management of chronic diseases. These efforts align with the sustainable development goal 3 (SDG 3); Good Health and Well-being, particularly Target 3.4, which aims to reduce premature mortality from non-communicable diseases through prevention and treatment by 2030.

Longevity-promoting interventions commonly entail functional trade-offs, raising the unresolved question of whether lifespan extension necessarily compromises physiological performance. Here, utilizing a chemically defined diet (CDD) in Drosophila melanogaster, we systematically evaluated a multimodal intervention combining methionine restriction (MR), taurine supplementation (Tau), and moderate exercise. This combinatorial approach additively extended lifespan, preserved reproductive capacity,...

Aging is commonly framed as a progressive accumulation of cellular and tissue-level damage. However, the aged organism does not decline as a collection of isolated organs. Aging is communicated systemically through blood-borne signals that connect senescent cells, immune remodeling, vascular dysfunction, metabolic stress, dysbiosis, and chronic inflammation. I propose the concept of the circulating senosome to describe the composite network of age-associated circulating mediators, including...

Aging is characterized by progressive loss of proteostasis, and heat shock transcription factor 1 (HSF1) is the master regulator of the cellular stress response, making it an attractive pharmacological target for interventions aimed at extending lifespan. However, a systematic synthesis of phytochemicals that modulate HSF1 has been lacking. Following PRISMA 2020 guidelines, we systematically searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library from March 2016 to March 2026,...

Age-related disease burden accumulates heterogeneously from later midlife to older age, but the biology underlying these divergent trajectories is poorly understood. We analysed 7199 adults aged 40 years and over in the Tsuruoka Metabolomics Cohort Study, Japan, with baseline fasting plasma metabolomics (94 metabolites measured by capillary electrophoresis-mass spectrometry) and linked health insurance claims. Monthly cumulative Charlson Comorbidity Index scores were constructed from aligned...

Chloride is the most abundant anion within lysosomes and plays a pivotal role in regulating lysosomal physiology and function. However, the mechanisms governing lysosomal chloride homeostasis remain largely elusive. Here, we identified TTYH3 as a regulator of lysosomal chloride permeability. TTYH3 mediates chloride efflux from the lysosomal lumen and enhances TRPML1-mediated lysosomal calcium release. Overexpression of TTYH3 results in markedly enlarged lysosomes by promoting lysosomal fusion...

Chemoresistance in pancreatic ductal adenocarcinoma (PDAC) is partly driven by pathological stromal remodeling, yet the underlying mechanisms remain poorly understood. Here, we show that gemcitabine treatment induces tumor cell senescence and activates cancer-associated fibroblasts via the senescence-associated secretory phenotype, leading to progressive fibrotic matrix stiffening. This biomechanical reprogramming engages the mechanosensitive ion channel Piezo1, triggering metabolic rewiring...

Alzheimer's disease (AD) is a common age-related neurodegenerative disorder (NDD), with ageing as its primary risk factor. Cellular senescence, characterized by permanent cell-cycle arrest, apoptosis resistance and acquisition of the senescence-associated secretory phenotype (SASP), is the cellular hallmark of ageing. Recent evidence indicates that blood-brain barrier (BBB) dysfunction precedes cognitive decline and pathological protein deposition, representing an early event in AD, with the...

CONCLUSIONS: Physical activity is closely associated with lower health inequality among older adults in China, especially among physiologically vulnerable and socioeconomically disadvantaged groups. Policies promoting accessible community-based physical activity may help improve health equity in aging populations.

ObjectivesSibling ties are among the most enduring of all social relationships, so the loss or absence of this long-standing bond may undermine the well-being of older adults. This study examined whether and how disconnectedness from adult siblings (i.e., no contacts/interactions and emotional distance) is linked to older adults' cognitive functioning.MethodsWe use data from four waves of the Wisconsin Longitudinal Study (1993-2020) and structural equation models to prospectively evaluate the...

Peripheral nerves regulate skin homeostasis by secreting neurotransmitters, but their role during skin aging remains incompletely understood. Here, we report that cutaneous denervation accelerates skin aging, as evidenced by collagen reduction. Neurofilament heavy chain (Nefh) is decreased in aged skin and is predominantly expressed in vesicular glutamate transporter 2-positive (Vglut2^(+)) skin-innervating glutamatergic neurons. Notably, dermal fibroblasts, the primary producers of collagen,...