Aging & Longevity

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CONCLUSIONS: We present a real-life baseline study on centenarians. Our findings contribute to understanding extreme longevity and may facilitate future studies, progress in healthcare, lifestyle decisions, and societal policies that benefit long-lived people.

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Vitamins are essential metabolites that must be obtained from external sources. In modern times, they have become widely available, leading to their ad hoc consumption. We developed a nutritional genomics framework to systematically identify monogenic diseases responsive to micronutrient modulation. Genome-wide CRISPR screens under varying vitamin B2 and B3 levels revealed dozens of candidate disease genes amenable to rescue by individual vitamins. In the vitamin B3 screen, NAD(P)HX dehydratase...

Frailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min...

The physiological effects of spaceflight resemble those of ageing and prolonged inactivity, and ground-based microgravity analogs have emerged as promising models for studying frailty. The human microbiome is increasingly recognised for its role in age-associated decline, although precise mechanisms remain unclear. Here, we evaluate the gut and oral microbiomes of twenty-two participants, aged 55-65, who were enrolled in a head-down tilt bedrest (HDBR) study, the first Canadian HDBR study...

Programmed cell death-1 (PD-1) is a co-inhibitory receptor expressed on T cells that dampens TCR and CD28 signaling in the immunological synapse. PD-1 is significantly upregulated on T cells in the tumor microenvironment, where it promotes exhaustion in the context of chronic antigen restimulation. Exhaustion renders T cells hyporesponsive and ineffectual, but potentially resistant to restimulation-induced cell death (RICD). Restimulation-induced cell death (RICD) is a critical propriocidal...

Systemic inflammation ("inflammaging") accelerates biological aging and drives cardiovascular, metabolic, and neurodegenerative disease. Circadian rhythms regulate the amplitude and timing of immune responses, yet their mechanistic role in inflammation and longevity remains unexplored. In 62,000 adults with 7-day wearable accelerometry, interpretable machine learning model identified rhythm amplitude, stability, and moderate-to-vigorous physical activity (MVPA) as dominant predictors of...

Simple performance-based tests such as gait speed, the Five-Times-Sit-to-Stand Test (FTSST), balance tests, and handgrip strength are associated with health outcomes. We aimed to establish age- and sex-specific reference (normative) values for these tests in the English population. Adults aged ≥ 50 years (female n = 4,234; male n = 3,424) from the English Longitudinal Study of Ageing were included. Weighted percentiles ranging from the 5th to the 95th percentile [P5-95] were calculated. Best...

Exercise, a well-recognized non-pharmacological anti-aging strategy, is key for human health. Growing evidence points to exhaustive or strenuous exercise, especially when recovery is inadequate, may trigger oxidative damage and accelerate aging. This study aims to systematically the effects of exhaustive and/or strenuous exercise on aging-related molecular and physiological biomarkers using a systematic review and meta-analysis. A systematic literature search was conducted across PubMed,...

Intrinsic capacity (IC), a composite measure of physical and mental capacities, reflects the functional manifestations of biological aging, yet large-scale population evidence on how IC varies throughout adulthood outside Western settings remains limited. Using data from 17,086 Chinese adults aged 25-89 years in the nationally representative PENG ZU cohort, we characterized age-related variation in IC and its associated factors. IC was assessed across five domains (locomotion, cognition,...

Long-lived wild rodents closely related to laboratory mice on the evolutionary scale may allow identification of dormant pathways that resist aging. Spiny mice (Acomys) are known for their exceptional regenerative capacity, but their resilience to aging is unknown. Here, we report that aged golden spiny mice (Acomys russatus), reared in a non-pathogen-free environment, resist functional decline, have a greater repair capacity with reduced senescence in immune-metabolic organs compared to their...

The blood-brain barrier (BBB) is crucial for brain homeostasis, and its dysfunction is associated with aging and neurodegenerative diseases. A recent seminal study by Shi et al. (2025) published in Nature illuminates a previously underappreciated component, the brain endothelial glycocalyx, as a key player in age-related BBB breakdown. They demonstrated that aging and neurodegenerative disease can lead to significant structural and compositional dysregulation of the brain endothelial glycocalyx,...

The existence of human hippocampal neurogenesis has long been disputed^(1-12) and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer's disease (AD)^(11,13). However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with...

Transposable elements (TEs) in the human genome are the heritage of ancient parasitic infections. While most of human DNA comprises TEs and TE-derived elements, their repetitive nature poses technical challenges; thus, little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigate when, where and how TEs become part of a gene. We characterize how TE-derived isoforms change across mouse-human...

Biological aging reflects complex cellular and biochemical processes that can be measured across multiple omic layers. Using routine clinical laboratory data from ~31,000 participants in the Mass General Brigham Biobank, we developed EMRAge, a biomarker of mortality risk that can be broadly recapitulated across electronic medical records. Here we show that EMRAge can be modeled using elastic net regression with DNA methylation and multi-omics to generate DNAmEMRAge and OMICmAge, respectively....

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan,...

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Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...