Aging & Longevity

Lower socioeconomic position (SEP) is related to poor health, and epigenetic aging represents a potential mechanism of action. We aimed to estimate associations between a novel measure of SEP and epigenetic age in a nationally representative cohort. We used data from NHANES survey waves 1999-2000 and 2001-2002. Our exposure was a novel three-category indicator of SEP, incorporating income, wealth, occupational status, and educational attainment. Our outcomes included 13 different epigenetic...

The mitochondrial prohibitin (PHB) complex is essential for mitochondrial homeostasis, yet its depletion produces opposite effects on lifespan: shortening it in wild-type C. elegans but extending it in insulin/IGF-1 receptor daf-2 mutants, which show an attenuated mitochondrial unfolded protein response (UPR^(mt)). To identify regulators of this differential stress response and its role in aging, we conducted the first genome-wide double-RNAi screen in C. elegans. We identify the...

Patients with chronic traumatic brain injury (cTBI) experience long-term exacerbated neurological decline, which is even more severe in older patients, yet the underlying mechanisms remain unclear. Cranial bone marrow (CBM) has recently been recognized as an adjacent immune surveillance organ of the brain that rapidly responds to acute brain injury. We investigated whether CBM-derived immune cells contribute to chronic neuroinflammation after cTBI by integrating clinical specimens, cell-tracing...

Currently, no generalizable tools exist for predicting the impact of interventions on aging using gene expression changes. Here, we build a model for predicting potential geroprotectors by deconstructing the aging transcriptome into coexpression modules and identifying those modulated by life span-extending interventions in Caenorhabditis elegans (C. elegans). Many of these modules exhibited adaptive changes during aging that are linked to longevity. Using these longevity-associated modules, we...

Biological aging clocks offer estimations of aging and dementia, yet scalability is limited. We introduce a large-scale, cross-national speech clock derived from 2928 individuals across five Latin American countries, spanning healthy controls (HCs), mild cognitive impairment (MCI), Alzheimer's disease (AD), and non-language/language-dominant frontotemporal dementia (nldFTD/ldFTD). Multimodal acoustic and linguistic features were trained with supervised models to estimate chronological age,...

CONCLUSION: These findings tie signBrake performance costs to weaker preparatory control differentiation and altered post-stimulus dynamics that support braking under interference. This reduced flexibility may contribute to age-related declines in driving safety in moments that call for rapid, goal-directed control.

Notch1 and vascular endothelial growth factor-A (VEGF-A) are polyfunctional signaling molecules that can be activated in response to elevated shear stress. In nonpathological conditions, they are integral to healthy endothelium; however, it is unknown whether their responsiveness during aerobic exercise, a robust shear stimulus, is impacted by age. Accordingly, in this exploratory cross-sectional study, concentrations of VEGF-A and Notch1 extracellular domain (NECD) were quantified in...

Alzheimer's disease remains a major neurodegenerative disorder for which effective disease-modifying treatments are limited. Adeno-associated virus-mediated gene therapy provides a strategy for sustained modulation of disease-related pathways in the central nervous system. Recent studies have explored this approach for regulating amyloid-β (Aβ) metabolism, tau pathology, neuroinflammation, genetic risk factors and neurotrophic support. This review summarizes the biological basis for...

Mitochondrial dysfunction drives scleroderma pathogenesis. The mitochondria-associated endoplasmic reticulum membrane (MAM) regulates mitochondrial function. Parthenolide (PTL) has protective effects on mitochondria. However, its specific role and mechanisms in localized scleroderma (LoS) remain unclear. This study investigates whether PTL reduces senescence and skin fibrosis by stabilizing MAM in LoS and examines the protective effects of a synthesized thermosensitive controlled-release...

Aging is accompanied by progressive immune remodeling and functional decline across multiple organs. However, the role of neutrophils and their heterogeneous states in these processes remains incompletely understood. Here we integrated single-cell RNA sequencing datasets from multiple organs of young and aged mice to characterize aging-associated neutrophil remodeling. We identified organ-dependent changes in neutrophil abundance and state composition, together with neutrophil subsets enriched...

Skeletal muscle aging is increasingly recognized as a failure of tissue-level coordination rather than a consequence of isolated defects in individual cell types. Recent advances in single-cell, spatial, and multimodal omics have revealed that aging remodels the abundance, functional states, and interactions of muscle-resident populations, shifting the tissue from a regenerative niche toward a degenerative niche. In this Review, we summarize current evidence supporting this conceptual transition...

Oligodendrocytes (OLs) are brain cells that make myelin, the insulating sheath that supports nerve signal transmission. Although oligodendrocyte dysfunction is common in the central nervous system (CNS), how these cells respond to injury remains incompletely understood. Here we show, using mouse models and mouse tissue analyses, that OLs respond to demyelinating diseases by increasing the expression and secretion of serine protease inhibitor clade A member 3N (SERPINA3N). This transition of...

Algal-bacterial interactions regulate the production and fate of marine particulate organic carbon (POC), yet their capacity to generate long-lived carbon sinks remains unclear. Using a two-year, nutrient-self-sustaining co-culture of Synechococcus and its mutualistic microbiota, we demonstrate that sustained algal-bacterial interactions promote the progressive accumulation of recalcitrant POC. Continuous release of algal-derived organic substrates, coupled with repeated microbial enzymatic...

Chronic stress-induced osteoporosis is a prevalent yet therapeutically challenging condition, with sympathetic overactivation as a key contributor. The dominant pathological mediator and strategies for its precise, non-invasive modulation remain unclear. Here, we identify sympathetic neuropeptide Y as a critical driver of this pathology. Using an unpredictable chronic mild stress model in male mice, we show that neuropeptide Y directly induces cellular senescence in bone marrow adipocytes,...

Aging paradoxically leads to both a decline in skeletal muscle mitochondrial function and a shift in muscle composition that favors fibers rich in mitochondria. Yet the biological rationale and mechanism underlying this phenomenon remain largely unknown. Here we show that synthesis of the mitochondrial membrane lipid, cardiolipin, causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. By mimicking the aging decline of skeletal muscle...

Extracellular vesicles (EVs) have been proposed to be mediators of the health-promoting effects of exercise throughout the body, but how EVs communicate these beneficial signals to recipient cells remains unknown. Here we interrogated these mechanisms using articular cartilage as a model. Network propagation of EV microRNA perturbations on a cartilage-specific network identified microRNA-29 as an exercise-responsive regulator of cellular aging. Consistent with this prediction, a 3-month aerobic...

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Evidence suggests that age-associated differences in body composition-bone/muscle/adipose tissue-are nonlinear, but their timing, sex-specific features, and relation to osteosarcopenic adiposity (OSA) phenotype remain poorly defined. OSA is characterized by the coexistence of osteopenia/osteoporosis, sarcopenia, and excess or redistributed adiposity. We examined sex- and age-specific patterns and inflection points for bone, muscle, fat, and intramuscular adipose tissue (IMAT) in cross-sectional...

Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype,...

AMP-activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing; however, most in vivo drug studies rely on the use of indirect activators, such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in...