He et al. characterizes a role of microcephalin (MCPH1), a known regulator of DNA damage response, in hematopoietic stem cell (HSC) aging demonstrating nuclear MCPH1 translocation that leads to activation of necroptosis and deterioration of HSC function with age.

Circulating factors have an important role in aging. Here the authors show that small extracellular vesicles derived from young plasma rejuvenate whole-body physiology in aged mice, at least in part, by stimulating PGC-1α expression and improving mitochondrial energy metabolism.

The Muscle Aging Cell Atlas presents approximately 200,000 single-cell and single-nuclei transcriptomes from 17 human donors across different ages, uncovering mechanisms of aging in muscle stem cells, myofibers and microenvironment cells, and demonstrates parallels in mouse muscle aging.

Lipid changes across the lifespan and their role in health and longevity are incompletely understood. Here, Tsugawa and colleagues conduct untargeted lipidomics across 13 sample types and four ages in mice, considering sex and microbiome dependencies. This study provides a comprehensive resource of lipid changes with aging and highlights regulatory metabolic components, such as the enzyme UGT8, as potentially responsible for male-specific glycolipid biosynthesis in the kidney.

Liu et al. identify downregulation of DDX5, an RNA helicase, in the cartilage of patients and mouse model of osteoarthritis. Targeted upregulation of DDX5 in mouse chondrocytes inhibits hyaline cartilage fibrosis and degradation via pre-mRNA splicing and G4 unwinding, a potential therapeutic strategy against osteoarthritis.

Moses, Atlan et al. profile the killifish (Nothobranchius furzeri) gonad using single-cell sequencing and reveal that genetic germline depletion induces sexually dimorphic phenotypes, enhancing lifespan in male fish and somatic repair in females.

Tong et al. construct simulations using DNA methylation data to quantify what proportion of the predictive accuracy of epigenetic clocks could be explained by stochastic methylation changes, suggesting that stochasticity contributes more toward the accuracy of chronological rather than biological age predictions.

Cellular senescence is a hallmark of aging but also a potent tissue remodeling process. Here, Nehme et al. show that modulating poly (ADP-ribose) polymerase 1 can switch cell death into senescence, and that inducing senescence improves recovery from kidney ischemia–reperfusion injury.

Bian, Zhang, Guo, Li, Fu et al. present results of a parallel-group, cluster-randomized controlled trial demonstrating the efficacy of an educational intervention targeting college students in increasing COVID-19 booster vaccination uptake among grandparents in China.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

Artificial intelligence (AI) chatbots offer the potential to enhance many aspects of social care for older adults, but also pose ethical risks. This Comment explores the responsible use of AI chatbots, which recognizes the distinct features of social care provision.