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.

Profiling the human thymus and peripheral blood, Deng and colleagues demonstrate impaired T cell development and compromised thymic microenvironment during aging, reveal inflammatory characteristics of T cell aging and generate a naive T cell-based model for immune age prediction.

In their study, Ezuz et al. show that the aged spleen contributes to T cell aging through hemolytic stress and an increasingly heme- and iron-rich microenvironment. T cells adapt by limiting their iron levels. This protective response impairs cell function but can be reversed in vivo by iron supplementation during activation.

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.

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.

Biofluid and imaging biomarkers for Alzheimer’s disease can identify disease pathology in cognitively unimpaired people, a substantial proportion of whom will not clinically express the disease. The International Working Group offers a risk stratification framework for management directed at the prevention of the clinical expression of Alzheimer’s disease.