Aging & Longevity

CONCLUSIONS: Multicomponent non-pharmacological interventions may provide cognitive benefits, particularly for memory and executive function, though certainty varied and findings from lower-quality reviews should be interpreted cautiously.

The global prevalence of aging and age-related diseases has increased markedly in recent decades due to extended life expectancy and a growing aging population, posing substantial medical and social burdens. Multiple strategies, including metabolic modulation (e.g., physical exercise, calorie restriction, and calorie restriction mimetics), targeting inflammaging, senotherapy, parabiosis, stem cell-based therapies, and epigenetic rejuvenation, have shown promise in slowing aging and extending...

β-Hydroxy-β-methylbutyrate (HMB), a bioactive leucine metabolite, has emerged as a potentially valuable nutritional compound with effects extending beyond skeletal muscle metabolism toward systemic immunometabolic regulation. This review summarizes evidence from 24 experimental and clinical studies regarding the potential relevance of HMB to brain aging and age-related disorders, with emphasis on mitochondrial regulation, inflammatory signaling, redox homeostasis, and exercise-associated...

Telomere shortening drives hair follicle senescence, yet successful reversal of this aging process has remained elusive. Here, we report that stem cell overexpression of Acd, the gene encoding TPP1 (telomere protection protein 1)-a shelterin component that recruits telomerase-accelerates hair regeneration in mice. Stabilization of TPP1 protein via topical application of TELODIN, a synthetic octapeptide that inhibits TPP1 degradation, similarly promotes hair regeneration. Mechanistically,...

The stepwise movement of oxygen from the atmosphere to the mitochondria, the "oxygen cascade", is one of the most tightly regulated systems in physiology. Despite decades of mechanistic study, it has remained quite unexplored in Geroscience. This oversight should be reconsidered. In young organisms, hypoxic stress (whether environmental or tissue-specific) activates a complex adaptive response to preserve energetic stability via restraining anabolic pathways, optimizing mitochondrial...

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Traumatic brain injury (TBI) is a major cause of mortality and persistent neurological disability and is increasingly recognized as a potential contributor to accelerated brain aging and long-term neurodegenerative processes. Beyond the immediate mechanical insult, TBI initiates dynamic secondary injury cascades involving chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, synaptic and axonal degeneration, metabolic disturbances, and blood-brain barrier disruption. The...

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....