Seo et al. present a cerebrospinal fluid (CSF) proteomic profiling of cognitively normal individuals, identifying age-associated, sex-associated, APOE ε4-associated and amyloid-associated changes. They unveil early Alzheimer’s disease CSF-specific proteomic signatures and potential therapeutic targets.

Sekiya and colleagues identify that, in response to reductive metabolism, CtBP2 is secreted via exosomes and regulates metabolism in recipient cells via CYB5R3 and AMPK. Exosomal CtBP2 administration extends lifespan and healthspan in aged mice, and serum levels of CtBP2 decline with age in humans.

Elyahu and colleagues describe the reciprocal interplay between senescent cells (SCs) and a helper T cell population that accumulates during aging. They show that selective depletion of this T cell population increases SC accumulation, accelerates frailty and limits lifespan in mice.

This genomic study of magnetic resonance imaging-based brain age in 56,348 people identifies 59 genetic loci, links brain aging to mental and physical health, and suggests high blood pressure and type 2 diabetes as causal factors of brain aging.

In cross-sectional and longitudinal analyses of 86,149 participants across 27 European countries, Amoruso, Hernandez and colleagues identify multilingualism as a protective factor against accelerated aging, using biobehavioral age gaps.

Methylation of nucleolar ribosomal DNA shifts during aging and in cellular senescence. Yan and colleagues engineer sensitive and photostable rRNA-selective dyes and present a fluorescence lifetime imaging strategy to quantify aging and senescence in cells, tissues, C. elegans, mice and human samples.

Infectious diseases can cause acute seizures. Here the authors investigate their long-term impact on the risk of epilepsy for older adults. They find that hospital-treated infectious diseases have a lasting impact on the development of epilepsy in older age, and that cardiovascular risk factors may exacerbate this impact.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

Parsons and colleagues characterize age-associated changes in the tumor microenvironment of triple-negative and estrogen receptor-positive breast cancer using computational analysis of transcriptomic data, paired with immunostaining of independently collected samples.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

Through biological, functional and psychosocial pathways that include inflammation, malnutrition and social isolation, oral health and disease contributes to systemic aging and frailty. Building on the concept of oral frailty, here we argue that validated oral health indicators — which are widely captured in aging surveys — should be integrated into multidimensional frailty frameworks to improve prediction, early intervention and holistic care for older adults.

Dementia is a rapidly growing healthcare issue in Africa, a region challenged by limited resources and lack of awareness. The World Health Organization (WHO) Regional Office for Africa introduces and explains the WHO regional policy framework for mental health, and neurological and substance use conditions in their efforts to tackle dementia in the region.