Using a dimensionality reduction approach, Fong et al. generated a clinical aging clock (PCAge) that delineates healthy and unhealthy aging trajectories. They provide a streamlined version (LinAge) that maintains predictive power, and they demonstrate how the clock can be tailored to available data using the CALERIE study.

Ibanez et al. performed a scoping review and meta-analysis of healthy aging studies across Latin America and report substantial heterogeneity in how risk factors affect cognitive and functional ability, underscoring the need for further regional research.

Using an iterative boost and transplantation model to generate multilifetime T cells, Mi et al. show that cellular epigenetic age can be uncoupled from organism age. While naive T cells appear epigenetically young, memory T cells and T-ALL leukemia can exhibit epigenetic ages exceeding the organismal lifespan.

Thermogenic beige adipose tissue can enhance energy expenditure and improve metabolism, but its formation declines with age. Park, Hu et al. show that replenishing estrogen can restore cold-induced beige adipogenesis by regulating NAMPT-controlled ER stress.

Using machine learning techniques applied to multimodal UK Biobank data, Wen et al. characterize the genetic basis of the biological age gaps of individual organs, uncovering interorgan cross-talk and links between chronic diseases, lifestyle factors and biological age gaps.

Using longitudinal data from the ELSA-Brasil study, Gonçalves et al. report that income is a barrier to how adherence to the sustainable planetary health diet is linked to slower cognitive decline.

Age-related immune dysfunction can compromise immune responses to infection and vaccine efficacy. Across two cohorts, Dallan et al. demonstrate that protective immunity against severe acute respiratory syndrome coronavirus is optimally maintained in older adults after primary adenoviral immunization (ChAdOx1-S) and subsequent mRNA vaccine boosting (BNT162b2 or mRNA-1273).

The mechanisms underlying susceptibility to metabolic dysfunction-associated steatotic liver disease (MASLD) in aging are incompletely understood. Here the authors show that an aging hepatocyte gene signature is enriched in MASLD liver tissue and contains ferroptosis genes. Experiments in mice show that metabolic stress increases ferroptosis in liver tissue in old compared to young animals and that blocking ferroptosis in old animals reduces the susceptibility to metabolic stress.

Here the authors show that deep learning accurately predicts one-year mortality using nationwide Finnish data. Despite robust performance and potential as an aging marker, fairness analyses reveal prediction disparities, urging cautious integration into public health.

Using single-nucleus RNA sequencing data from patients with sporadic amyotrophic lateral sclerosis (ALS) cortices, the authors find that higher expression of ALS risk genes is accompanied by upregulation of stress responses in groups of extratelencephalic neurons. Analyses of glial nuclei revealed a downregulation of myelination genes in oligodendrocytes and upregulation of reactive state genes in microglia.

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.