Aging & 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...

No abstract

Pain is the leading cause of disability worldwide, yet no harmonized self-reported reference framework exists to characterize how its burden is distributed across the lifespan and world regions. In this study, we harmonized individual-level self-reported pain data from 6,125,459 participants across 902 population-based data sources in 118 countries to establish global reference trajectories of pain. We implemented these trajectories in an open-access benchmarking platform for positioning...

CONCLUSIONS AND IMPLICATIONS: Most factors associated with fall-related head impact were nonmodifiable (eg, sex). Training the use of protective fall movements, environmental design (including protective equipment), and education hold promise in reducing the risk of head impact. Future research should prioritize testing modifiable approaches in real-world settings for reducing fall-related head impact and, ultimately, preventing head injuries in the aging population.

Veterans experience mild traumatic brain injury (mTBI) at significantly higher rates than civilians, alongside high rates of comorbid conditions such as PTSD, mood disorders, and alcohol abuse. These conditions have documented impacts on brain health that compound with age. Prior work has demonstrated reduced white matter (WM) integrity and greater age-related trends in WM deterioration in Veterans with mTBI compared to Veterans without mTBI. These studies provide important insights, yet were...

CONCLUSIONS: In this exploratory, partially randomized comparison, TUG-derived dual-task gait cost decreased more in the NMES group, but the marked baseline imbalance limits causal interpretation. DTC appears feasible and potentially responsive as an outcome for future fully randomized sham-controlled rehabilitation trials.