Ming, Yang, Huang et al. design a chimeric matchmaker peptide, which targets a senescent cell-specific surface marker and modifies the cell surface with polyglutamic acid. This promotes interactions with natural killer cells and senescent cell clearance in liver fibrosis, lung injury, cancer and natural aging.

Intrinsic capacity includes a person’s mental and physical capacities. The authors examined cohort trends in intrinsic capacity in two large English and Chinese studies. They report that more recently born participants entered older ages with markedly higher levels of functioning, while subsequent age-related declines were somewhat delayed.

The authors describe how aging rewires the cellular composition of mouse mammary tissues and impacts the transcriptomic and epigenomic programs of mammary epithelial, fibroblast and immune cells, identifying shared signatures of aging and cancer.

Arora et al. present AgeXtend, an explainable artificial intelligence-based platform that leverages bioactivity data to predict geroprotectors. They validate potential geroprotectors identified using this platform in yeast, worm and senescence assays.

Using single-cell imaging of a fluorescent chaperone-mediated autophagy (CMA) reporter and RNA sequencing data, the authors present a resource on basal CMA activity across organs, cell types and sexes in young and old mice, offering a comprehensive overview of changes in this proteostatic mechanism in the context of aging.

Using multi-omics analysis, Zuo, Zhao, Wu, Wang, Wang and colleagues report disrupted branched-chain amino acid (BCAA) catabolism in skeletal muscle samples from patients with sarcopenia. In mouse models, they causally link BCAA catabolic dysfunction to impaired muscle mass and demonstrate the translational potential of enhancing BCAA catabolism.

Applying epigenetic clocks to samples from the DO-HEALTH trial, Bischoff-Ferrari et al. report a small protective effect of omega-3 supplementation over 3 years on several clocks and an additive protective effect of omega-3, vitamin D and exercise using PhenoAge.

Yang, Jn-Simon, He et al. report that the dual BCL-xL/BCL-2 PROTAC 753b is a potent and liver-tropic senolytic, which (unlike other inhibitors of BCL-xL) does not cause severe thrombocytopenia. They evaluate its efficacy in natural aging and in reducing progression from steatotic liver disease to hepatocellular carcinoma, using mouse models.

Lee et al. demonstrate that Ginkgolide B treatment extends lifespan and enhances healthspan in female mice, including a reduction in tumor incidence, enhancement in muscle quality and function and suppression of systemic inflammation and senescence.

Toghani, Gupte et al. identify semaphorin 4A as a cell-extrinsic factor that protects myeloid-biased hematopoietic stem cells from inflammaging, mainly produced by their progeny—neutrophils—and acting via a negative feedback loop.

Geriatric day hospitals were originally set up to provide rehabilitation and social care for older adults. Román Romero-Ortuño highlights how in Ireland, geriatric day hospitals have evolved into hubs for integrated care, which prevents avoidable hospital admissions and promotes independence for older adults.

Although the emerging field of geroscience holds great promise for identifying new approaches to improve healthspan, several risks of the current framework are underappreciated. Long time horizons, challenges in identifying causality-driven surrogate biomarkers of aging, and the potential for biological trade-offs and antagonistic effects across various timescales mean it will be hard to know when such interventions have a net benefit. We propose eight strategies to mitigate these risks going forwards.

Reproductive aging is increasingly recognized as an important determinant of fertility span and overall health and wellbeing in older age. In this Focus issue, Nature Aging presents a series of reviews and opinion pieces on recent advances in reproductive aging research.