Aging & Longevity

CONCLUSION: Health literacy is a key factor of active and successful ageing. To promote active ageing, older adults care centres should prioritise health literacy.

Hutchinson Gilford progeria syndrome (HGPS) is a fatal premature aging disorder caused by pathogenic farnesylated lamin A variants that disrupt nuclear architecture and DNA repair. Current therapies, including farnesyltransferase inhibitors, provide only modest survival benefits and lack molecular specificity, while mutation-specific genome-editing strategies cannot address atypical laminopathies. Here, we develop Farnesylation Amino acid Targeted Editing (FATE), a mutation-agnostic base-editing...

Estrogen Receptor alpha (ERα) is the primary driver in ER+ breast cancer and can be targeted using small molecules such as fulvestrant, a selective estrogen receptor degrader (SERD). Despite being approved over two decades ago and used regularly in post-menopausal women, its precise anti-tumor mechanism remains unclear, with several reports showing efficacy without the requirement for ERα degradation. To investigate the molecular basis of fulvestrant's action, we employed split intein-based µMap...

Ageing has been described through many theoretical frameworks, yet its mechanistic basis remains unresolved. Here we propose that ageing reflects progressive decanalization of mammalian cell identity, driven by erosion of a regulatory grammar written during development. Extending Waddington's epigenetic landscape, development canalizes cell fates through globally coordinated chromatin programs that establish identity constraints across multiple timescales. Subsequently, these constraints can...

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Neurotoxicity refers to injury of the central or peripheral nervous system caused by harmful stimuli including environmental chemicals, disease-associated endogenous stressors and other exposures that disturb neuronal homeostasis. A common outcome of neurotoxic stress is progressive disruption of synaptic function, redox balance and energy metabolism which together increase vulnerability to regulated cell-death programs. This review focuses on oxidative stress as core driver that shift reactive...

Epstein-Barr virus (EBV) infects most humans and persists lifelong within a dynamic equilibrium maintained by B-cell latency, cytotoxic T-cell control, NK-cell surveillance and humoral immunity. Ageing can remodel this equilibrium through thymic involution, contraction of the naive T-cell pool, accumulation of late-differentiated or exhaustion-like T-cell states, altered NK-cell function, B-cell dysfunction and chronic low-grade inflammation. Although cytomegalovirus has dominated discussions of...

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...