Aging & Longevity

Microglia, the resident immune cells of the central nervous system, dynamically respond to signals from their microenvironment, including adjacent neurons. Among these signals, nuclear contents released from damaged neurons have been implicated in triggering inflammatory microglial responses. Recently, we found that micronuclei (MNs) derived from neurons during the early postnatal stage act as intercellular mediators that alter the microglial characteristics. However, it remains unclear whether...

White matter (WM) abnormalities have emerged as a critical element in Alzheimer's disease (AD) pathogenesis, shifting from their former status as a passive consequence to an active contributor to disease progression. Notably, microstructural WM alterations, detectable early via advanced neuroimaging techniques such as diffusion tensor imaging, frequently precede overt gray matter atrophy and cognitive decline, highlighting their potential as early contributors to AD pathogenesis. The origins of...

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and predominantly affects older individuals, yet effective treatments remain limited. The molecular mechanisms linking cardiac aging to HFpEF are not fully understood. Here we show that the transcriptional regulator Sub1 is upregulated in aged hearts and in mouse models of HFpEF. Cardiac overexpression of Sub1 shortens lifespan, exacerbates diastolic dysfunction, and accelerates...

Cellular aging is accompanied by progressive alterations in metabolic homeostasis, stress adaptation, and organelle function. Increasing evidence suggests that functional coordination among membrane-bound organelles, including mitochondria, the endoplasmic reticulum (ER), lysosomes, peroxisomes, and the Golgi apparatus, contributes to cellular homeostasis during aging. However, the mechanisms linking kinase signaling to specific inter-organelle contact sites or communication pathways remain...

CONCLUSIONS: In humans, available evidence suggests that nutritional interventions may preferentially affect senescence-associated inflammatory and secretory biomarker profiles, particularly SASP-related mediators, rather than markers more directly related to senescent cell abundance. However, because SASP factors and circulating cytokines are heterogeneous and not specific to senescent cells, these findings should be interpreted as evidence for possible modulation of senescence-associated...

CONCLUSIONS: We unveiled the critical role of Sirt3 in maintaining mitochondrial homeostasis and mitigating intervertebral disc degeneration progression via regulating Ckm and Atp2a1. We provide a novel therapeutic strategy of activating of Sirt3 by 2-APQC to treat intervertebral disc degeneration.

Chyawanprash is an ancient Ayurvedic superfood described for its antioxidant, anti-ageing and immunity-boosting properties. Prolonged exposure to environmental stressors such as extreme heat, air pollution and toxins could lead to several diseases by triggering oxidative stress and inflammation. These stress response pathways, conserved in humans and C. elegans, play crucial roles in the progression of neurological and metabolic diseases. Present study examines the role of the ancient Ayurvedic...

Brain maintenance - the preservation of brain structure or function relevant to cognitive performance - remains challenging to quantify. Here, we propose a domain-general brain maintenance index derived by jointly modelling the longitudinal co-evolution of ageing-related atrophy (via medial temporal lobe to ventricle ratio, MTLV-ratio), white matter hyperintensities (WMH), and global cognition assessed by the preclinical Alzheimer's cognitive composite (PACC5) using latent growth curve...

Biological age often diverges from chronological age, yet its independent impact on surgical outcomes remains poorly defined. We evaluated PhenoAge, a validated biological age metric, in an international multi-cohort study comprising over 430,000 surgical patients across the UK, USA, and South Korea. In the UK Biobank (N = 291,845), PhenoAge was a robust, independent predictor of 1-year mortality (OR 1.043; p < 0.001), major adverse cardiovascular events (OR 1.041; p < 0.001), and 30-day...

CONCLUSION: This study demonstrate that it is urgent to involve community pharmacies into age-friendly initiatives, to create safe environments for older population which is one of the most frequent patients in community pharmacies.

CONCLUSIONS: Lower SHR values were associated with increased vulnerability to geriatric syndromes, particularly probable sarcopenia and frailty, in older adults. These findings suggest that SHR may reflect impaired metabolic adaptation and reduced physiological reserve in aging populations. Further prospective studies are needed to establish the clinical utility of SHR as a marker of geriatric vulnerability.

CONCLUSIONS: Physical frailty was associated with lower IL-17 and higher TGF-β1 levels, suggesting that immune-related pathways beyond classical systemic inflammation may be associated with physical frailty. Rather than reflecting overt systemic inflammation, these findings suggest that biological pathways involved in immune regulation and tissue remodeling may be associated with physical frailty. IL-17 and TGF-β1 may therefore represent potentially informative biomarkers for future...

Loneliness and social isolation increase the risk of physical and mental disorders in older adults, while resilience may mitigate this risk. The evidence that medial temporal lobe (MTL) structures are associated with loneliness, social isolation, and resilience is largely cross-sectional. This study examined whether baseline MTL structures were associated with loneliness, social isolation, or resilience during the COVID-19 pandemic. 114 older adults (59 females; mean age: 73.8 ± 5.6 years)...

Two principal strategies have gained prominence among currently recognised approaches to anti-ageing: systemic interventions that modulate the circulatory environment and cellular interventions that reset epigenetic information. Systemic approaches, beginning with experimental heterochronic parabiosis models that are not applicable to humans and extending to clinically applicable therapeutic plasma exchange, test the hypothesis that ageing is promoted by the accumulation of inhibitory...

Tumors reprogram lipid metabolism in distant tissues to support their growth. In adult Drosophila, gut tumors secrete the PDGF/VEGF-like factor Pvf1, which activates the TORC1-Hnf4 pathway in hepatocyte-like oenocytes. This drives production of very long-chain fatty acids and wax esters essential for tracheal growth around the tumor. Blocking Hnf4 or the elongase mElo in oenocytes strongly suppresses tracheogenesis, tumor progression, and cachexia-like organ wasting, while extending host...

Autosomal dominant mutations in TARDBP, encoding TAR DNA-binding protein 43 (TDP-43), cause amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is a hallmark of multiple aging-associated neurodegenerative diseases. Despite its pathological role, effective therapies remain limited by the lack of safe, potent molecules targeting TDP-43 neurotoxicity. Here we show that the conserved α-helical region spanning residues 320-340 (conserved region or CR) is a therapeutically actionable target for...

Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy...

The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression-both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related...

Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL...

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a...