Aging & Longevity

The growing evidence that existing cardio-renal-metabolic therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, confer all-cause mortality benefits has positioned them as the first wave of potential gerotherapeutics. However, repurposing these drugs for a lifespan extension indication remains constrained by trial duration, misaligned incentives, and the lack of a viable regulatory path. We highlight two parallel strategies to address these barriers: (1) identifying and validating...

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The steroid hormone dafachronic acid may carry the effects of reduced mTOR activity between tissues to coordinate metabolism and longevity across the body.

Advanced brain age relative to chronological age may predict cognitive decline in healthy aging, but prospective evidence remains limited. We tested whether the brain age gap (BAG) predicts cognition and 5-year cognitive decline in the AGES-Reykjavik Study. Participants with structural MRI and neuropsychological data were included cross-sectionally (n = 4,606); mean age 76.4y; 58% female) and longitudinally (n = 2,561; mean follow-up 5.2y). BAG was estimated from T1-weighted MRI. Mixed-effects...

Cellular senescence is characterized by coordinated disruptions in mitochondrial function and epigenetic regulation, with perturbation of the mitochondria-chromatin axis emerging as a central hallmark of this process. Resveratrol (RSV) has been extensively investigated as a modulator of this axis; however, its clinical utility is constrained by dose-dependent cytotoxicity. Here, we evaluated the safety profile and anti-aging potential of resveratrol glucoside (R-glc), a glucosylated derivative...

Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in...

Cytotoxic chemotherapy typically results in the elimination of a fraction of the tumor with surviving cells entering a state of persistence or premature replicative senescence that can lead to recurrence. Here, we show that therapy-induced senescence is associated with robust up-regulation of Fas and/or TRAIL-R2/DR5 death receptors in vitro and in vivo. The latter receptors restricted entry to senescence and exerted selective pressure on senescent cells through promoting assembly of proapoptotic...

Inflammaging, a state of chronic low-grade inflammation, is a key contributor to biological aging and diabetes. Traditional inflammatory indices within the interplay between inflammation and epigenetic aging have remains insufficiently explored. In addition, novel platelet-based inflammatory indices based on platelets may perform better than traditional inflammatory indices. This study was a cross-sectional study with survival analysis and analyzed data from 2494 participants in the National...

Neuronal senescence, triggered by oxidative stress and inflammatory responses, is a significant risk factor for brain aging, ultimately leading to cognitive decline. Apelin-13, an exercise-induced myokine, exhibits potential neuroprotective effects by the APJ system, but its protective effects against neuronal senescence and the underlying mechanisms are unknown. This study aimed to elucidate how apelin-13 prevents D-galactose-induced neuronal senescence in SH-SY5Ys, human induced pluripotent...

Moderately cold temperatures extend lifespan and promote health across species^(1-3), yet the molecular mechanisms underlying these benefits remain unclear. Here we define a metabolite-driven, multi-tissue signalling system that links cold temperature to enhanced longevity and proteostasis in Caenorhabditis elegans. Cold temperature upregulates the biopterin-synthesis enzyme CAT-4 (GCH1 in humans), increasing production of dihydrobiopterin (BH2), a transportable reservoir for the bioactive...

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CONCLUSION: While dietary diversity improved similarly in both arms, the intervention-specific improvement in LLMS - a parameter associated with functional capacity - suggests the ALAPAGE program has potential as a preventive public health approach for contributing to healthy aging in community-dwelling older adults.

CONCLUSIONS: Older people with Parkinson's described contending with the progressive nature of Parkinson's and the erosion of independence, while informal caregivers reported the physical, emotional and financial burden of caregiving. Care work was becoming more difficult, yet families in this study demonstrated adaptability, resilience and enduring obligation to enact and reciprocate care. This study emphasises the need to strengthen, support and sustain community-based approaches to care for...

CONCLUSION: A substantial proportion of stroke survivors did not achieve the targets recommended by the ESO for secondary prevention. In the older people population, fewer patients reached optimal blood pressure control, and anticoagulant use among those with atrial fibrillation was suboptimal. Our findings highlight the need for structured post-stroke follow-up pathways, improved communication between stroke specialists and primary care physicians, and targeted interventions to optimize...

CONCLUSION: This cross-sectional study found a significant association between proximity to major roadways and prevalent diabetes in Chinese older adults. Roadway proximity acts as a composite surrogate marker of traffic hazards, neighborhood socioeconomic deprivation and built environments, rather than merely traffic pollution or noise. These findings guide future environmental and health equity research on seniors. Longitudinal studies with objective exposure measurements are required to...

Nicotinamide adenine dinucleotide (NAD^(+)) is an essential metabolite that regulates diverse cellular metabolic processes. Primary cilia, hair-like organelles on the cell surface, function as critical signaling hubs. Here, we demonstrate that cellular NAD^(+) levels are key regulators of both primary cilia growth and lysosomal function in hypothalamic neurons. NAD^(+) depletion induces ciliary shortening and diminishes lysosomal activity in a cilia-dependent manner. Mechanistically, the...

Calcific aortic valve disease (CAVD) is an age-associated valvular disorder in which calcification expands from discrete foci into adjacent tissue. We investigated whether mitochondrial-derived vesicles (MDVs) released by human valvular interstitial cells (hVICs) exert pro-calcific effects on recipient cells and how MDV release is regulated. Using ex vivo hemodynamic perfusion of human CAVD tissue, multi-omics profiling, live-cell single-organelle tracking, MDV transfer assays, and in vivo Gas6...

Patients with idiopathic pulmonary fibrosis (IPF) are highly vulnerable to respiratory virus infections, but the cellular mechanisms linking fibrotic remodeling to impaired local antiviral defense remain unclear. Here, we investigated how cellular senescence shapes the response of patient-derived healthy (HLF) and IPF primary lung fibroblasts to influenza A virus (IAV) infection. Transcriptomic profiling identified infection as the driver of gene expression in both DNA damage-induced senescent...

INTRODUCTION: Easy-to-Read (E2R) formatting is widely recommended to improve reading accessibility, yet whether its typographic and structural features benefit visual processing and comprehension across the adult lifespan remains unclear.