Aging & Longevity

Aging is a major risk factor for the formation, growth, and rupture of intracranial aneurysms, but the underlying biological mechanisms remain incompletely understood. Beyond chronological aging, accumulating evidence suggests that vascular aging is driven by cellular senescence, chronic inflammation, and hemodynamic stress, which together contribute to aneurysm wall degeneration. In this review, we synthesize current evidence on the role of aging in intracranial aneurysm biology, with a...

We are racing towards a time wherein the largest demographic of the population will be comprised of older adults and where it is now also possible to measure, monitor, and diagnose long term risk factors and provide effective and valuable preventative interventions. Thanks to the achievements of modern health care, we have reached a tipping point in the need for a robust geriatric workforce. Through the implementation of thoughtful, deliberate, and collaborative processes, Artificial...

Under-recognition of cognitive impairment remains a major global public health challenge, particularly in low- and middle-income countries. Many cases go unrecognised because conventional cognitive assessment is resource-intensive and difficult to scale across diverse populations. Here we show that easily captured indicators of reduced survey response quality, derived from how older adults answer routine psychosocial questionnaires, can identify cognitive impairment risk across countries. Using...

Aging is accompanied by widespread DNA methylation changes, yet their full genomic scope and parent-of-origin dynamics remain poorly understood. Here, we apply nanopore long-read sequencing to 7,284 whole blood samples enabling methylation measurements of 17,959,684 high-quality CpG units. Over 20% of the measured high quality CpG units undergo age-associated changes, predominantly hypomethylation. From these data, we construct a methylation aging clock from 1,373 high-quality CpG units, with...

The cholinergic system is central to attention, learning, and neuroplasticity and undergoes progressive degeneration with aging. Neuroplasticity-based computerized cognitive training is a scalable, non-pharmacological strategy to support cognitive health in older adults, yet its neurobiological mechanisms remain unclear. [18F]Fluoroethoxybenzovesamicol (FEOBV) positron emission tomography (PET) quantifies presynaptic cholinergic terminals via vesicular acetylcholine transporter (VACht) binding,...

Microtubules are well-researched components of the cytoskeleton, yet we lack a holistic understanding that bridges molecular and cellular details with the broader functions of the microtubule cytoskeleton in development, ageing and disease. For example, how microtubule properties and functions are affected by tubulin post-translational modifications, disease-related mutations or variation of the microtubule lattice remains unexplored. In this Roadmap, we argue that integrating various...

Breast cancer is among the leading causes of cancer mortality worldwide, with aging as a major risk factor. Caloric restriction (CR) is a well-established non-pharmaceutical intervention that extends healthspan and delays tumorigenesis, yet the systemic molecular mechanisms remain elusive. Both chronic and intermittent CR influence metabolic homeostasis, but their long-term effects on circulating miRNAs in breast cancer predisposition are unclear. Here, we examined how chronic and intermittent...

Secreted proteins are essential to modulate homeostasis in the extracellular space and facilitate communication to distal cells or tissues. Yet, the identity and functional importance of extracellular proteins in aging have been understudied. Here we use proximity labeling followed by quantitative proteomics to systematically characterize proteins along the intestinal secretory pathway in C. elegans, focusing on secreted proteins. We identify intestine-secreted proteins that are modulated with...

Can the skin microbiome shape healthy aging?

Skeletal muscle is the main motor organ and plays a vital role in regulating systemic metabolism and aging. Exercise interventions can address many metabolic and degenerative diseases associated with aging, though alternative strategies may be needed when exercise is contraindicated, inaccessible or insufficient. Here we developed subcutaneous transplantation of differentiated autologous myocytes (myografts). Myografts exhibited mature, vascularized structures that self-contract continuously in...

Inflammation is a pivotal driver of the progression from metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH), an aggressive form associated with substantial liver-related mortality. However, the molecular mechanisms underlying the initiation and persistence of liver inflammation remain poorly defined. Here, we demonstrated a previously unrecognized role for hepatic acetyl-CoA synthetase short-chain family member 2 (ACSS2) in...

Interest in aging 'omic' biomarkers has grown due to their ability to quantify biological age. Most of these biomarkers have been derived in blood and fall into many diverse categories, yet relatively little is known about their correlative patterns, especially between biomarkers from different categories. Here we present the OmniAge R and Python package, a collection of 413 aging omic biomarkers representing 12 different categories, including traditional epigenetic clocks, epigenetic mitotic...

Human cells utilize gut microbiota-derived metabolites to control systemic metabolism. Trimethylamine N-oxide (TMAO) is traditionally considered a hepatocyte-derived metabolite from microbial trimethylamine. Here we show that pancreatic β-cells also produce TMAO as an autocrine and intracellular metabolite to maintain β-cell function. β-cells synthesize TMAO via flavin-containing monooxygenase 3 (FMO3), but this machinery deteriorates in humans and rodents under diabetic and ageing conditions....

The genus Myotis is one of the largest clades of bats, and it exhibits some of the most extreme variation in lifespans among mammals, alongside unique adaptations to viral tolerance and immune defence^(1-3). Here, to study the evolution of these phenotypes, we generated cell lines and near-complete genome assemblies for eight closely related Myotis species. Using genome-wide screens of positive selection, analyses of structural variation and functional experiments in primary cells, we identify...

No abstract

Age-associated hematopoietic skewing results in an increase in the neutrophil-to-lymphocyte ratio, which serves as a strong predictor of all-cause mortality in older adults, although its causes are incompletely understood. Here we show that cytotoxic CD4^(+) T lymphocytes accumulate in the bone marrow of mice during aging and induce myelopoiesis, increasing the neutrophil-to-lymphocyte ratio. T cell receptor-dependent induction of mitochondrial stress and activation of STING upregulates the...

The associations between objectively measured sleep patterns, the hallmarks of aging, and their shared proteomic signatures remain poorly understood. In this study, we utilized wrist-worn accelerometer data, plasma proteomic profiles, and health records from the UK Biobank to examine the associations between six defined sleep patterns and nine established hallmarks of aging. We further identified proteins jointly associated with both sleep patterns and aging hallmarks. Longer total sleep...

Genotoxic stress induced by cancer therapies is increasingly recognized as a driver of accelerated aging in long-term cancer survivors, yet the mechanisms responsible for the emergence of age-related dysfunction months to years after treatment remain poorly understood. Here, we use sublethal whole-body irradiation as a model of systemic genotoxic stress to test whether senescent cells contribute to the progression of post-therapy age-related dysfunction and whether the benefits of senescent cell...

Sarcopenia is the age-related progressive decline in both skeletal muscle mass and function. It acts as an exacerbator of multimorbidity, engaging in bidirectional pathological cycles with multiple chronic diseases, and contributes substantially to increased mortality, disability and healthcare costs. Current nutritional support is often limited by a generic one-size-fits-all approach that fails to account for substantial inter-individual variation across genetics, metabolism, lifestyle, gut...

CONCLUSIONS: CNN-derived masseter muscle parameters from magnetic resonance imaging were inversely correlated with oral impairment in older adults. This approach enables scalable and objective oral phenotyping from imaging data and highlights its potential application in large-scale epidemiological studies of aging and functional decline.