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Vitamin B2 and B3 nutrigenomics reveals a therapy for NAXD disease
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...
Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty
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...
Effect of bedrest on the human gut and oral microbiome: implications for frailty
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...
PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling
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...
From wrist data to lifespan: elucidating inflammation-driven biological aging via activity rhythms captured by wearable devices
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...
Reference values for gait speed, five-times-sit-to-stand test, balance, and handgrip strength: analysis of data from the English Longitudinal Study of Ageing
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...
Daily briefing: Stem-cell treatment strengthens people with age-related frailty
World-first stem-cell therapy shows promise for treating spina bifida in the womb
Neanderthal dad, human mum: study reveals ancient procreation pattern
Ultra-sensitive CAR T cells eliminate hard-to-treat tumours in mice
Subtyping Alzheimer’s disease and Parkinson’s disease using longitudinal electronic health records
Private money cannot replace public funding of science
Science, Volume 391, Issue 6788, February 2026.
Erratum for the Report “Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations”
Science, Volume 391, Issue 6788, February 2026.
Cryo–electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2
Science, Volume 391, Issue 6788, February 2026.
Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging
Science, Volume 391, Issue 6788, February 2026.
Reconstitution of sex determination and the testicular niche using mouse pluripotent stem cells
Science, Volume 391, Issue 6788, February 2026.
Different DNA repair pathways support intact or truncated insertions by R2 retrotransposon protein
Science, Volume 391, Issue 6788, February 2026.
A cellular basis for the mammalian nocturnal-diurnal switch
Science, Volume 391, Issue 6788, February 2026.
Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds
Science, Volume 391, Issue 6788, February 2026.
STING–NF-κB signaling builds an influenza spillover barrier
Science, Volume 391, Issue 6788, February 2026.