Volume 5 Issue 10, October 2025

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.

Attempts to translate senolytics from preclinical models to humans are gaining momentum. Early clinical trials have provided positive biological signals, but we lack clear evidence for the efficacy of senolytics in humans. Based on what we have learned in these initial trials, it may be time to aim for a more personalized approach in designing future senolytic trials, and potentially also in the eventual clinical use of these compounds.

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.

A leader in geriatric medicine and aging biology and champion of the constructs of frailty and resilience.

Bai and colleagues show that specialized translation hubs called mitochondria-associated translation organelles (MATOs) form by liquid–liquid phase separation on the mitochondrial surface. MATOs congregate ribosomes and specific mRNAs to supply key proteins on-site and thereby uphold mitochondrial integrity and function. Persistent association of MATOs with mitochondria enhances stress resistance and extends lifespan.

Nicotinamide adenine dinucleotide (NAD⁺) decline is a molecular characteristic of aging and age-associated neurodegenerative diseases. Lee and colleagues uncover an astrocyte-specific regulatory axis directed by the circadian clock component REV-ERBα, and provide proof-of-concept evidence that targeting this pathway alleviates tauopathy in mouse models.

Using genome-wide analyses in over 56,000 individuals, we identify 59 genetic loci linked to brain aging, of which 39 are novel. This work also uncovers key biological pathways that connect brain aging to mental, metabolic, cardiovascular and lifestyle factors, and offers insights for promoting healthy aging and preventing neurodegenerative diseases.

Single-nucleus transcriptomic and histopathological analyses of the cochlea of aged macaques identified multiple features of degeneration, including accelerated hair cell loss, senescence of spiral ganglion neurons with neuroinflammation, and stria vascularis atrophy. Of note, reduced protein levels of a transmembrane transporter are a pivotal molecular signature of hair cell aging.

Meyer and colleagues refute the idea that, as aging can be tracked precisely by clocks, it must be driven by a biological program. They propose that imperfect maintenance and repair processes resulting from a selection shadow facilitate the accumulation of stochastically occurring damage, which in turn advance the aging process with the precision of a clock.

The authors identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that increases with age and promotes cognitive decline. Targeting FTL1 in the brain improved cognition in old mice.

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.

Membraneless organelles formed by liquid–liquid phase separation regulate cellular processes. Here Bai et al. show that mitochondria-associated translation organelles (MATOs) consisting of RNA-binding proteins and translation machinery mediate localized synthesis of mitochondrial proteins to promote mitochondrial health and extend lifespan in worms.

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.

Declining oocyte quality contributes to age-related reduction in fertility; however, the underlying mechanisms are incompletely understood. Here Liu et al. reveal that replenishing mevalonate pathway metabolites and supplementation with a natural compound, 8-isopentenyl flavone, improve aged oocyte quality by restoring cortical F-actin through CDC42 and RAC1 prenylation.

Hu et al. identify border-associated macrophages as early targets of brain aging. These cells acquire senescence-associated properties, which are transmittable via migrasomes carrying the apoptosis inhibitor of macrophage. Blocking migrasome production attenuates cognitive decline in aged mice.

Bodogai et al. identify a unique subset of CD8⁺ T cells expressing CD39 and CD73 that accumulate during aging and are recruited to and actively promote tumor progression by suppressing antitumor CD4⁺ T cells. Targeting their function or recruitment attenuates tumor growth in aged mice.

Lee et al. show that the circadian clock protein REV-ERBα controls brain NAD⁺ levels by regulating the NAD⁺-consuming enzyme CD38. Global or astrocytic REV-ERBα deletion or pharmacologic REV-ERB inhibition protects against tau pathology 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.

Afshar, Dammer et al. identify plasma proteins associated with Alzheimer’s disease brain pathologies and find that many plasma proteins related to cognitive function are not associated with these pathologies.

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.