Aging & Longevity

Stroke is one of the leading causes of mortality and disability worldwide, with ischemic stroke accounting for over 87% of all stroke cases. Chronic kidney disease (CKD) is one of the major risk factors for stroke, as CKD patients have shown evidence of impaired cerebral autoregulation leading to exacerbated stroke pathology. The worsening of stroke outcomes in CKD patients is limitedly understood. Inflammation plays a pivotal role in driving the CKD-stroke pathology. The cGAS-STING (cyclic...

Intrinsic capacity is a concept established by the World Health Organization (WHO). The concept aims to represent the total of a person's physical and mental abilities, measured across five domains: cognition, psychological, sensory, vitality, and locomotor that were identified as crucial for healthy aging. The aim being to shift focus from disease to function to predict health, disability, and frailty. In this large-scale cohort study, we aim to investigate the association between intrinsic...

Ageing is accompanied by declining memory function, with extremely heterogeneous manifestation in the human population¹. Brain-extrinsic factors influencing cognitive decline, such as gastrointestinal signals, have emerged as attractive targets for peripheral interventions^(2-6), but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which...

Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood¹. Here we show that ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic dissemination through epigenetic activation of the integrated stress response (ISR). The ISR effector ATF4 drives epithelial and metabolic plasticity, conferring metastatic competence. Mechanistically,...

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Major depressive disorder (MDD) is associated with widespread alterations in functional brain networks across the lifespan. However, heterogeneity in atypical brain development among patients with MDD remains largely uncharacterized. Using a multisite resting-state functional MRI dataset consisting of 1,105 MDD patients and 1,065 healthy controls, we constructed a harmonized multicenter brain age prediction model based on individualized functional topography and identified two patient subgroups...

Phenotypic heterogeneity is prevalent during aging, yet its underlying molecular drivers remain poorly understood. In budding yeast, two distinct aging trajectories, characterized by either ribosomal DNA (rDNA) instability or mitochondrial decline, have been proposed to be mutually exclusive. Here, we systematically dissect the heterogeneity among aging yeast cells by combining single-cell transcriptomics with longitudinal fluorescence microscopy. Our data reveal distinct transcriptional...

The EAT-Lancet diet (ELD) and plant-based diets (PBDs) are recommended for their potential health and environmental benefits, but comparative analyses of these dietary patterns in relation to mortality risk remain limited. This study aimed to evaluate the associations of ELD and PBDs with mortality and life expectancy in two nationwide cohorts. Participants from the UK Biobank and the US National Health and Nutrition Examination Survey (NHANES) (2003-2018) were included. Dietary intake was...

Sex-specific trajectories of vascular aging may influence stroke recovery, yet their impact on access to reperfusion and long-term outcomes remains uncertain. We analysed 3760 consecutive patients with angiography-confirmed cerebral vessel occlusion transferred for endovascular therapy (EVT) between 2015 and 2022. Women accounted for 45.1% of patients and were significantly older (median 77 vs. 70 years) with greater baseline stroke severity (NIHSS 14 vs. 12). Access to acute stroke care was...

Cellular senescence, originally described as a finite proliferative arrest in cultured somatic cells, has since been recognized as a central mechanism underlying aging and the development of age-associated disorders. The progressive accumulation of senescent cells (SnCs) promotes chronic inflammation through the senescence-associated secretory phenotype (SASP) and circumvents immune-mediated clearance by upregulating pro-survival and immune checkpoint pathways. Early "first-generation"...

A growing body of evidence supports the role of nutrient sensing and metabolism pathways in regulating ageing rate and healthspan, but the diversity of human lifestyles challenges our ability to identify the mechanisms of this age acceleration. Here, we examine how the transition of wild King penguins to zoo husbandry can closely mimic the shift to a Western lifestyle in humans, and shed light on conserved epigenetic changes in responses to sedentary conditions. We show that, just like modern...

Cellular morphology is tightly linked to function, but how subcellular transcript localization contributes remains unclear. Using microglia, the brain's resident macrophages, as a model, we combined multiplexed error-robust fluorescence in situ hybridization with immunohistochemistry to map how morphology and subcellular mRNA localization interact with function in young and aged mouse brains. We show that mRNA spatial organization varies across microglial states and defines distinct localization...

The postmenopausal decrease in estrogen production contributes to a significant increase in the risk of age-related diseases. There is an identified gap in the field regarding the effectiveness of targeted interventions for specific groups of women at increased risk, and whether these interventions can support successful aging and reduce mortality. Data regarding 2239 Caucasian female participants of the PolSenior study aged 65 and over were analyzed. Based on strict criteria, participants were...

CONCLUSIONS: This work establishes a valuable transcriptomic resource for glial GABA-associated ASH neuronal aging and identifies candidate pathways, offering critical molecular insights to dissect age-related neurodegeneration mechanisms and inform potential therapeutic targets.

Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of the optic nerve, or glaucoma. Although macrophages reside throughout the conventional outflow tract, their role in regulating intraocular pressure remains unknown. Using macrophage lineage-tracing approaches, we uncovered a dual macrophage ontogeny with distinct spatial organization across the mouse lifespan. Long-lived resident tissue macrophages were...

Histone modifications represent an untapped resource for biological age prediction that overcomes limitations of traditional DNA methylation-based epigenetic clocks. Here, we developed and validated histone modification-based epigenetic clocks by systematically analyzing publicly available ChIP-seq datasets spanning six tissue types and six histone marks. We identified age-associated loci and constructed 36 tissue-specific epigenetic clocks that demonstrated strong resilience to technical and...

Infraslow (<0.1 Hz) global brain activity, quantified by the global mean blood-oxygenation-level-dependent (gBOLD) signal in resting-state functional magnetic resonance imaging (fMRI), is elevated during sleep and coupled to cerebrospinal fluid (CSF) dynamics, a key pathway for the brain waste clearance implicated in neurodegenerative disorders such as Alzheimer's disease. However, the effect of sleep deprivation on gBOLD activity and its interaction with aging remain poorly understood. Using a...

Parental age and inbreeding have both been shown to have substantial fitness effects in laboratory experiments and in observations of wild animals. These demographic effects are likely to be strongly impacted by habitat fragmentation and warming temperatures, so understanding them is a priority. In insects and other ectotherms, some processes implicated in senescence are dependent on temperature. Anticipated changes in climate may therefore have direct effects on senescence in insects, or...