Aging & Longevity

Higher-order chromatin structure is linked to cell differentiation and aging, but its native distribution in tissues and role in organismal development remain unclear. Here, we introduce SpaceA, a spatial omics approach for in situ chromatin architecture profiling. Compared with high-throughput chromosome conformation Capture (Hi-C), SpaceA captures substantially more contacts over distances beyond 10 Mb, thereby enhancing detection of higher-order chromatin dynamics. Applied to nine mouse...

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality, with substantial residual risk persisting despite contemporary lipid-lowering, antithrombotic, and anti-inflammatory therapies. Increasing evidence indicates that vascular smooth muscle cells (VSMCs) actively shape plaque composition, progression, and stability through cellular programs that partially resemble those involved in tumor evolution. Within this framework, tumor-like transformation...

Aging is characterized by profound biological changes, among which epigenetic remodelling -encompassing alterations in DNA methylation patterns and microRNA modulation - and inflammaging (chronic, low-grade systemic inflammation) represent major contributors to functional decline and the pathogenesis of age-related diseases. While increasing evidence suggests a complex interplay between epigenetic modifications and inflammaging, a comprehensive elucidation of this axis remains elusive. In this...

This study examined short-term trends in the prevalence of major chronic diseases, multimorbidity patterns, and of healthy aging levels among older adults participating in free health checkups in Longhua District, Shenzhen, from 2022 to 2024. Using random sampling, 10,000 participants were selected annually from the elderly health management information system, and both crude and age-standardized rates were calculated. Changes in prevalence were assessed using the Mantel-Haenszel test and...

CONCLUSION: Together, these findings indicate that lifespan divergence in N. furzeri is associated with distinct mitochondrial aging trajectories, supporting that enhanced antioxidants defenses and mitochondrial quality control contribute to the preservation of brain mitochondrial homeostasis and increased longevity.

Canine models are invaluable for translational geroscience, but natural sex-associated immune aging remains under investigated. Here, we characterize the age-associated hematologic and serum cytokine profiles in a controlled cross-sectional cohort of 80 intact laboratory Beagles spanning 1 to 11 years of age. Canine immune aging is heterogeneous and non-linear. While several absolute leukocyte counts declined with age before rising again in geriatric dogs, serum cytokines exhibited distinct,...

Systemic aging alters ocular structures and plasma metabolome, yet relationships between multidimensional biological aging, environmental exposomes, plasma metabolism, and retinal changes remain uncharacterized. This study evaluated how these phenotypic networks align with retinal structural variations. Following rigorous screening, 45,542 UK Biobank participants (2006-2010) were analyzed. Systemic aging was quantified using PhenoAge acceleration, Klemera-Doubal method age acceleration (KDM-BA),...

γδ T cells have an unconventional biology as they develop as functional cells in the thymus, to thereafter adapt to postnatal cues and persist into adulthood in peripheral blood. Single-cell transcriptomics enables investigation of underlying molecular programs of γδ T cell effector functions in health and disease. However, the effect of age is often underestimated, and control transcriptome datasets of young healthy individuals are rare. Here, we generate a cost-effective single-cell...

CONCLUSIONS: CKMAI is a valid, CKM‑specific aging index that outperforms universal biological age measures in predicting mortality and identifying high‑risk CKM status. Its super‑additive interactions with PhenoAge and the partial mediation by depression offer new mechanistic insights into CKM heterogeneity. By integrating a diverse set of clinical laboratory measures, nutritional assessments, lifestyle factors, and social determinants of health, CKMAI provides a practical, implementable tool...

Late-onset preeclampsia (LOPE) is a major pregnancy complication characterized by hypertension and placental dysfunction, resolving only upon delivery. Here, we show that LOPE placentae undergo accelerated molecular aging, marked by telomere attrition, DNA damage, and trophoblast senescence. Using primary placental tissue and trophoblast organoids, we demonstrate oxidative stress as a driver of telomere shortening and angiogenic imbalance. Inflammation did not alter placental aging trajectories....

Brain ageing is a complex physiological process characterised by progressive structural and functional changes that often result in cognitive decline and reduced quality of life in the elderly. These changes are driven by multiple mechanisms, including synaptic dysfunction, oxidative stress, neuroinflammation, and impaired cellular homeostasis. Neuropeptides have emerged as important regulators of these processes. Among them, neuropeptide Y (NPY) has gained attention for its potential role in...

CONCLUSION: The maps document a WoS-derived and PubMed-verified literature corpus concentrated on TDP-43 and ALS/FTD and increasingly connected with cryptic RNA processing, condensate biology, nuclear transport, neuroimmune responses, and aging-related mixed proteinopathies. Because the corpus was conditioned by a title-level query containing named RBPs and by PubMed record verification, these patterns should not be interpreted as an unbiased ranking of RBP biology or as evidence of shared...

Aging is a major risk factor in the development of type 2 diabetes mellitus (T2DM). With age, pancreatic β-cells undergo functional and cell identity changes that can compromise insulin secretion, thereby contributing to impaired glucose tolerance and T2DM. However, glucose homeostasis also depends on pancreatic α-cells. Excessive plasma glucagon levels, along with impaired regulation of α-cell secretion, are involved in the pathophysiology of T2DM. Despite their importance, the effects of aging...

Senescent cells are a key driver of aging and contribute to many age-related diseases. Senolytics, agents that selectively eliminate senescent cells, offer a promising therapeutic strategy to treat age-related diseases but face significant barriers to clinical translation. Fisetin, a natural flavonoid senolytic, has progressed to clinical trials but is limited by suboptimal efficacy and poor bioavailability. To address these challenges, we developed two novel fisetin-derived flavonoid...

CONCLUSIONS: Healthcare access among adults aged 80 years and older is shaped by interacting digital, physical, relational, communicative, organizational, and age-related factors. Access was generally not perceived as completely impossible, but as dependent on timely appointments, digital or telephone support, physical capacity, family assistance, and the ability to navigate healthcare processes. These findings highlight the need for age-sensitive healthcare pathways, including simplified...

Traditionally viewed as a classic sentinel of innate immunity, Toll-like receptor 4 (TLR4) has emerged as a crucial pathological driver within the vascular endothelium, with its identity dictated by cell-type specificity, microenvironmental context, and fluctuating expression levels. This review critically examines the dual functional nature of endothelial TLR4, delineating how it transitions into a primary driver of vascular aging and organ-specific vascular pathologies. The profound spatial,...

Epithelial-mesenchymal transition (EMT) is a highly dynamic and plastic cellular programme essential for embryonic development, tissue repair and ageing, and it is co-opted in pathological conditions such as cancer and fibrosis. The continuum of intermediate states and pronounced cellular heterogeneity that characterize EMT have historically limited systematic investigation across regulatory layers, including the transcriptome, epigenome, proteome and metabolome. Recent advances in...

Chaperone-mediated autophagy (CMA), the first-described selective lysosomal degradation pathway, is distinguished from other degradative pathways by the unique mechanism by which substrates reach the lysosomal lumen: CMA relies on a cytosolic targeting chaperone and a lysosomal membrane receptor that doubles as a translocation complex. In this Review, we highlight recent discoveries of additional molecular components involved in CMA and describe how genetic and pharmacological modulation of CMA...

Large extracellular vesicles (lEVs) are heterogeneous structures with sizes that exceed 200 nm. Unlike small extracellular vesicles, which originate from either the endosomal system or the plasma membrane, most lEVs stem directly from the plasma membrane, although the various lEV subtypes have distinct biogenesis pathways. Emerging findings have helped to update lEV classification and have provided insights into lEV biogenesis, cargo, physiological functions and relevance in disease. Classical...

Autophagy dysfunction and senescence are established drivers of aging, but their potential interaction remains poorly understood. Here we show that age-related decline of chaperone-mediated autophagy (CMA), a pathway for selective lysosomal protein degradation, changes senescent cell properties and impairs their immune clearance. CMA-deficient cells undergo senescence but acquire proteomic, metabolic and secretory features resembling those in aged senescent cells. Their senescence-associated...