Reviews & Analysis

Aging is associated with biological processes (such as the accumulation of senescent cells) that are relevant to the development of cancer. Using genetically modified mouse models, we discovered that p16^high senescent cells with a secretory phenotype accumulate in the bladder during aging, which leads to cancer progression.

The authors offer a new energy-focused perspective on aging by introducing a brain–body model that positions the brain’s response to cytokine signals of hypermetabolism as a mechanistic link between the cellular hallmarks and organismal manifestations of aging.

There was a radical increase in record human life expectancy during the 20th century. A study by Olshansky et al., however, now suggests that similar progress in the 21st century is unlikely. Although further advances will be difficult to achieve, more optimistic alternative scenarios should also be considered that rely on historical evidence and experiences of vanguard groups at the subnational level.

Wang and colleagues investigate the effects of the follicular microenvironment on egg aging in mouse and demonstrate that it is possible to rejuvenate aged eggs by exposing them to a young follicular microenvironment.

Cancer and aging are inextricably linked conditions. However, whether cancer emerges as a byproduct of the aging process or whether aged cells themselves are prone to become neoplastic remains enigmatic. A study by Castro, Shindyapina and colleagues now provides support for the latter by demonstrating that in aged mice that spontaneously develop lymphomas, tumors originate from clonally expanded age-associated B cells.

Many people struggle to be physically active during the week. Research now shows that accumulating the recommended amount of physical activity within a shorter time period, such as the weekend, has benefits for brain health equal to those of a regular physical activity pattern, and that this reduces risk of brain disorders, depression and anxiety.

Insights into the Alzheimer’s disease blood proteome from a population-based cohort show how the serum levels of certain proteins change prior to diagnosis, how they overlap with signature changes in disease-relevant tissues, and how the association between certain proteins and the disease markedly shifts according to APOE-ε4 carrier status.

Biomarkers of aging have potential to accelerate the clinical translation of interventions that promote healthy aging but are currently limited to research. The authors identify six barriers to be overcome to enable biomarker translation, providing a roadmap to clinical implementation.

Cervical lymphatic vessels drain cerebrospinal fluid from the brain. A recent study reveals an aging-related disruption in the pumping action of lymphatic vessels that hampers lymph flow, which may prevent efficient brain clearance of potentially toxic proteins linked to neurodegenerative disease.

A study from Ru, Deng, Chen, Zhang and colleagues investigates how mutations in the mitochondrial genes Nd1 and Nd5 are inherited in mice. The authors report that increased maternal age strengthens purifying selection during postnatal oocyte development, probably through an increase in oocyte protein synthesis.

We quantified age-related changes in gene regulatory relationships across eight human tissues. Our results reveal that the gene–gene relationships that become stronger with age affect mostly genes that operate on the same cellular processes, whereas relationships that become weaker affect genes involved in different processes.

Income is a modifying factor in the association between increased adherence to the planetary health diet and slower cognitive decline observed in a sample of 11,737 Brazilian civil servants who were followed for 8 years. Thus, addressing the barriers posed by low income is vital when promoting healthy eating patterns.

We developed ‘imaging-based chromatin and epigenetic age’ (ImAge), a technique that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei. We propose that ImAge represents a first-in-class imaging-based biomarker of aging with single-cell resolution.

The Integrated Care for Older People program of the World Health Organization is intended as a catalyst to empower communities to cocreate personalized interventions and usher in an era of precision healthy longevity, in which the needs, values and preferences of older people are centered. A study from France now presents early screening data and reveals distinct phenotypic trajectories towards adverse outcomes.

In our study, we linked machine-learning-derived biological age gaps (BAGs) to common genetic variants in nine human organ systems, which revealed how these BAGs are causally associated with organ health and chronic diseases such as Alzheimer’s disease and diabetes. The findings provide insights into therapeutic and lifestyle interventions that might enhance organ health.

A study from Ortega-Molina and colleagues uses mouse models with mildly elevated mTOR activity to investigate the stepwise process by which increased nutrient signaling affects healthy aging. These findings show how initial parenchymal damage caused by mTOR activity is followed by secondary myeloid inflammation, a multistage process that culminates in organ deterioration and reduced lifespan.

Our study shows that older adults who survive severe COVID-19 suffer accelerated cognitive decline for 1 year after infection, after which the rate of decline decelerates. Long-lasting cognitive impairment occurs mostly in individuals who had severe COVID-19, showed cognitive impairments at 6 months after infection and had coexisting hypertension.

SARS-CoV-2 infections are typically more severe with increased age. Vaccination can reduce morbidity and mortality, but the age-associated decline in immune function could limit vaccine efficacy in older adults. Dallan, Proietto and colleagues demonstrate robust immunological humoral and cellular memory in older adults who received primary vaccinations using the adenoviral platforms and received subsequent boosting with mRNA vaccine platforms.

Identification of patients at risk for hip fracture is crucial to inform intervention strategies. We developed a plasma protein-based risk score for hip fracture and validated this score in three independent cohorts using two substantially different proteomics platforms. The protein-based risk score, but not available polygenic risk scores, improved hip fracture discrimination.

A study demonstrates the efficacy of immune-checkpoint blockade in prolonging survival and boosting CD8⁺ T cell function in aged mice after pathogen exposure. These findings highlight how aging-related immune changes may lead to augmented CD8⁺ T cell responses to checkpoint blockade, which results in improved protection from infection. The findings also highlight the importance of understanding immune aging in future efforts to target immunotherapies to older adults.