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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...

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.

Science, Volume 391, Issue 6788, February 2026.