Reviews & Analysis

Age is a leading risk factor for osteoarthritis, a degenerative joint disease; however, the mechanisms by which degeneration occurs are not well defined. In this issue of Nature Aging, Wang, He, Gong and colleagues report that a specific palmitoyl acyl transferase, ZDHHC11, prevents cartilage degradation by modifying cellular senescence, which highlights its therapeutic potential.

A single blood-based test that measures several tau biomarkers enabled biological staging of Alzheimer’s disease. This approach not only indicated how advanced the disease was but also helped to predict its progression. This blood-based test could be highly valuable for patient management and for identifying individuals who are most likely to benefit from targeted therapies.

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.

On 12 February 2025, a joint meeting of the UK Aging Networks was held in Liverpool, UK. It was convened by the ECMage (extracellular matrix aging) network and EuroAgeNet, an initiative led by ECMage but involving four other UK aging networks — namely, the building links in aging science and translation network (BLAST), the cognitive frailty interdisciplinary network (CFIN), the aging and nutrient sensing network (AGENTS) and the food systems for older people (Food4Years) network — together with industrial and European partners. In this Meeting Report, we summarize the opinions of an industrial panel and round-table discussions on barriers and opportunities related to academic–industrial partnerships.

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.

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.

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.

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.

We developed a single blood-based methylation test that estimates biological aging across 11 physiological systems. This multisystem measure predicts mortality and health outcomes more precisely than existing epigenetic clocks, and reveals distinct aging patterns that could guide personalized gerotherapeutic and geroprotective interventions.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Levels of the metabolic coenzyme NAD⁺ decline during aging, which is linked to many age-related diseases. Zhang et al. review recent clinical and translational evidence testing NAD⁺ supplementation in age-related diseases, highlighting therapeutic challenges and opportunities.

Hearing loss is common among older adults and has reported associations with a higher risk of dementia. Machado-Fragua et al. offer evidence that shows midlife hearing loss is modestly associated with a higher incidence of late-life dementia, and highlight considerations of duration of exposure, measurement, intervention timing and public health awareness for dementia risk reduction.

Rechsteiner and colleagues explore how studying lifespan and disease resistance across species reveals natural adaptations that promote longevity. The authors summarize new discoveries and discuss approaches and recommendations for comparative aging research.

Analysis of granulosa cells from participants with age-related or pathological ovarian aging identified a crucial factor — NCOA7 — that promotes stress granule clearance via autophagy (‘granulophagy’), conferring protection against ovarian aging. Boosting NCOA7 activity or granulophagy alleviates senescence in granulosa cells and delays ovarian aging, suggesting new therapeutic strategies.

Vrtačnik et al. examined the contribution of accumulating somatic mutations to the decline in skeletal muscle function. They developed the ‘Muscle Somatic Mutator’ mouse model through targeted deletion of Msh2 and Blm, two important genes that are involved in DNA repair. They demonstrate that somatic mutations alone are sufficient to impair muscle strength and regeneration.

Inflammaging is a chronic, low-grade inflammatory state that is closely linked to aging; yet it is highly heterogeneous. Within the framework of personalized medicine, Franceschi and colleagues discuss measuring and treating inflammaging, highlighting the need for precision interventions.

Majewska and Krizhanovsky discuss the interactions of innate and adaptive immune cells with senescent cells, including mechanisms of clearance, evasion and paracrine senescence, as well as therapeutic strategies to restore surveillance in aging and disease.

Delgado-Pulido, Yousefzadeh and Mittelbrunn explore the molecular mechanisms by which adaptive immunity regulates the processes of aging, discussing age-related declines in protective functions and age-related gains of autoaggressive features in turn.

Hofer and colleagues explore how immunosenescence impairs vaccine efficacy in older adults, then review emerging vaccine technologies and gerotherapeutic interventions as strategies to enhance protective responses.

Weyand and Goronzy discuss how aging increases the risk for autoimmune disease. They propose that the inappropriate endurance of immune stemness predisposes older individuals to autoimmunity, as exemplified in patients with giant cell arteritis.