Aging & Longevity

Skeletal ageing involves changes in endocrine regulation, mechanical loading and cellular function that can impair bone remodelling. Cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as mechanisms that help close this gap. In the ageing bone microenvironment, senescent osteocytes, mesenchymal stem cells, osteoblasts, immune cells, and vascular endothelial cells secrete pro-inflammatory cytokines, chemokines, matrix metalloproteinases, and Wnt antagonists...

Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated with menopause and its links to brain aging. In n = 80 rigorously staged (STRAW+10) pre-, peri- and postmenopausal women (aged 43-58 years) with serum NULISAseq proteomics, we show that spontaneous menopause is characterized by...

Aging clocks are typically trained on pooled multi-tissue data, implicitly assuming that aging is uniform across organs. Here we challenge this assumption by constructing 49 transcriptomic clocks across 47 tissue types and 2 cell-line categories from GTEx v8 (948 unique donors contributing to the retained clock categories) using donor-grouped cross-validation. Clocks achieved a median Pearson r of 0.543 (best: artery aorta, r = 0.855). We identified 10,253 unique clock genes, of which 69.2%...

While osteoarthritis (OA) has traditionally been viewed as a localized joint disorder, systemic metabolic dysfunction is increasingly recognized as a key contributor to its pathogenesis. Here, we identify a liver-cartilage micronutrient axis in which hepatic dysfunction promotes OA through impaired selenium (Se) metabolism. Nationwide cohorts reveal elevated OA prevalence among individuals with liver disease. In murine models of acute and chronic liver injury and metabolic dysfunction-associated...

Immunosenescence-the age-associated remodeling of the immune system-has emerged as a potential modifier of chronic inflammatory disease. This review examines the evidence that immunosenescence may contribute to the chronicity, refractoriness, and therapeutic heterogeneity of uveitis, and considers the clinical and translational implications of this framework. It first outlines the features of immune aging, including thymic involution, contraction of the naïve T cell pool, accumulation of memory...

CONCLUSION: A significant correlation between fatigue (MF and SPF) and inflammation was found. Among the inflammatory biomarkers investigated, IL-6 showed the most consistent association with both MF and SPF across the included studies.

Intracerebral hemorrhage (ICH), caused by the rupture of blood vessels within the brain parenchyma, represents the most severe form of stroke, characterized by the highest mortality rate and predominantly affecting the elderly population. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as the resident immune cells of the central nervous system and undergo significant metabolic reprogramming following ICH. Microglia exhibit dual roles in post-ICH tissue damage by...

CONCLUSION: Sensory impairment, particularly dual sensory impairment, was most consistently associated with early cognitive deterioration and reduced cognitive recovery. It was not consistently associated with higher dementia progression or mortality transition rates. Death-inclusive multistate modeling may help identify where potentially modifiable sensory impairment is related to cognitive ageing trajectories.

INTRODUCTION: Despite growing interest in age-related cortical mechanisms of postural control, heterogeneity across studies has limited the synthesis of existing evidence. This systematic review aimed to (1) characterize age-related alterations in cortical activity during standing balance tasks with sensory, cognitive, and mechanical challenges; (2) examine the association between cortical activity and postural sway; and (3) characterize the current methodology of assessing cortical activity...

Aging is associated with declining protective immunity and increased autoreactivity, yet the mechanisms linking these processes remain incompletely understood. B lymphocytes are central to this paradox because they integrate antigen recognition, innate signaling, and differentiation under tightly regulated tolerance checkpoints. This review advances the hypothesis that aging appears to drive a progressive, B cell-intrinsic relaxation of central and peripheral tolerance, leading to the...

Mild cognitive impairment (MCI) represents a heterogeneous clinical state where some individuals remain stable while others progress to dementia. Identification of patients who are at high risk for near-term conversion remains a critical challenge for timely intervention. We developed an explainable multimodal machine-learning framework to predict progression from MCI to dementia within a clinically meaningful two-year period. We analyzed 2008 samples from 828 unique MCI subjects from the...

CONCLUSION: Faster gait speed was associated with a lower risk of mortality in adults aged 90 and older. These results were consistent across gender, race/ethnicity, and assistive device use, but differed by age group. Routine gait speed assessment may serve as a simple clinical tool to identify oldest-old adults at higher risk of mortality.

The nuclear hormone receptor NHR-49, a homolog of mammalian PPARα and HNF4α, is a key transcriptional regulator of nutrition sensing and fatty acid metabolism in Caenorhabditis elegans. Here, we examine the role of NHR-49 in reproduction, including oocyte activation and ovulation. Loss of NHR-49 causes inappropriate oocyte activation and laying of unfertilized oocytes in the absence of sperm, resulting in rapid loss of yolk and stored fat, and drastic shortening of lifespan. Conversely,...

Aging and tissue repair involve heterogeneous remodeling across transcriptional, biochemical and cellular dimensions, yet prevailing definitions rely on isolated molecular markers that obscure how these states co-evolve. Here we present RamanOmics, a multimodal framework integrating label-free hyperspectral Raman imaging with single-nucleus RNA sequencing and spatial transcriptomics to link biochemical states with transcriptional programs at single-cell spatial resolution. Applied to young and...

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Bilingualism has been proposed to confer advantages in cognitive aging, yet the neural mechanisms underlying any such advantages remain debated. In a pre-registered analysis of cross-sectional and longitudinal data from elders in the HABS-HD cohort, we asked whether bilingualism is associated with three measures of brain structure (total brain volume, hippocampal volume and white-matter lesions) and/or moderates the relationship between brain structure and two measures of cognition (executive...

Neurodegenerative diseases (NDs) are chronic neurological diseases characterized by progressive neuronal loss and pathological protein deposition in specific brain regions. With the deepening of population aging, these diseases have become one of the most serious public health challenges. Due to the high heterogeneity of these disorders and the complex pathogenesis, it brings great challenges to clinical precision diagnosis and treatment. In this context, nuclear medicine molecular imaging...

Handgrip strength asymmetry (HGSA) and low handgrip strength (LHGS) reflect distinct aspects of muscle health, but their changes over time have been less studied. We examined whether two-wave status patterns of HGSA and LHGS were associated with all-cause mortality in middle-aged and older Chinese adults. We analyzed 8924 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. HGSA and LHGS were assessed in 2011 and 2013 and classified as normal at both waves, newly...

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CONCLUSIONS: In this population-based cohort study, participation in a low-intensity preventive health program delivered in routine care was associated with a lower incidence of diabetes among older adults. However, the observational study design limits evidence on the intervention's role in the observed association, and more robust evidence is needed. Nevertheless, these findings suggest that scalable, population-wide prevention strategies may complement intensive high-risk approaches in...