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The Integrated Care for Older People program of the World Health Organization is intended as a catalyst to empower communities to cocreate personalized interventions and usher in an era of precision healthy longevity, in which the needs, values and preferences of older people are centered. A study from France now presents early screening data and reveals distinct phenotypic trajectories towards adverse outcomes.

The Integrated Care for Older People (ICOPE) program was developed to promote a function-centered and individualized approach to healthy aging, but it is not yet widely implemented. In this study, de Souto Barreto et al. used early-stage ICOPE data collected in primary healthcare from more than 20,000 older adults to characterize patterns of intrinsic capacity impairment and associated odds of frailty and disability.

Castro, Shindyapina et al. explore how aging promotes B cell lymphoma in mice, identifying a population of age-associated clonal B cells that expands through mutation, c-Myc activation and epigenetic alterations to drive age-associated malignancy.

In our study, we linked machine-learning-derived biological age gaps (BAGs) to common genetic variants in nine human organ systems, which revealed how these BAGs are causally associated with organ health and chronic diseases such as Alzheimer’s disease and diabetes. The findings provide insights into therapeutic and lifestyle interventions that might enhance organ health.

Mitochondrial DNA mutations are subject to purifying selection in the female germline, limiting the transmission of pathogenic variants. In this study, the authors used two mouse models that harbor pathogenic mutations in mitochondrial complex I and observed that maternal age intensifies purifying selection processes.

A study from Ortega-Molina and colleagues uses mouse models with mildly elevated mTOR activity to investigate the stepwise process by which increased nutrient signaling affects healthy aging. These findings show how initial parenchymal damage caused by mTOR activity is followed by secondary myeloid inflammation, a multistage process that culminates in organ deterioration and reduced lifespan.

Methionine restriction decreases fecundity and increases lifespan in flies. Here Wei et al. show that supplementing folic acid, associated with one-carbon metabolism, during methionine restriction in flies, mitigates the decline in fertility while retaining the intervention’s life-extending benefits.

This study reveals gut microbial and metabolomic features associated with the severity of frailty, demonstrating that these microbial features outperform traditional assessment tools in identifying individuals at high risk of frailty and mortality.

Our study shows that older adults who survive severe COVID-19 suffer accelerated cognitive decline for 1 year after infection, after which the rate of decline decelerates. Long-lasting cognitive impairment occurs mostly in individuals who had severe COVID-19, showed cognitive impairments at 6 months after infection and had coexisting hypertension.

Song et al. show that in young mice CD38 supports hematopoietic stem cell (HSC) proliferation by regulating Ca²⁺ signaling and mitochondrial activity. Conversely, the upregulation of CD38 during aging causes dysregulation of NAD metabolism, mitochondrial stress and HSC dysfunction.

Rejections by peer-reviewed journals are frequent, but authors may get a second chance to convince editors and peers by submitting an appeal. Here we explain how we approach appeals at Nature Aging and share some statistics on them to help authors to carefully consider when and how to appeal.

Zeng, Shi, Han, Hu, Li, Wei et al. present a metabolic atlas covering 15 hematopoietic cell types from young and aged mice. By screening metabolites that are depleted with age, they identify that uridine treatment can restore function in aged hematopoietic stem cells.

A Comment that discusses how biomarkers might be used in clinical practice to improve the diagnostic work-up of Alzheimer’s disease. It also highlights key knowledge gaps that need addressing before global clinical implementation of such markers.

SARS-CoV-2 infections are typically more severe with increased age. Vaccination can reduce morbidity and mortality, but the age-associated decline in immune function could limit vaccine efficacy in older adults. Dallan, Proietto and colleagues demonstrate robust immunological humoral and cellular memory in older adults who received primary vaccinations using the adenoviral platforms and received subsequent boosting with mRNA vaccine platforms.

Identification of patients at risk for hip fracture is crucial to inform intervention strategies. We developed a plasma protein-based risk score for hip fracture and validated this score in three independent cohorts using two substantially different proteomics platforms. The protein-based risk score, but not available polygenic risk scores, improved hip fracture discrimination.

Tracking cognitive function over 2.5 years following SARS-CoV-2 infection, Liu, Wu, Wang et al. find that cognitive decline in older COVID-19 survivors in Wuhan, China, manifests primarily in the first year following severe COVID-19.

Gadd et al. identify proteins circulating in the blood that can stratify the risk people have of developing a range of leading age-related diseases, up to a decade before onset.