Reviews & Analysis

On 16 and 17 March 2021, the National Institute of Allergy and Infectious Diseases and the National Institute of Aging convened a virtual workshop to discuss developments in SARS-CoV-2 research pertaining to immune responses in older adults, COVID-19 vaccines in both aged animals and older individuals, and to gain some perspective on the critical knowledge gaps that need addressing to establish scientific priorities for future research studies.

Age is the greatest risk factor for Alzheimer’s disease and aging is associated with the shortening of telomeres, the terminal regions of chromosomes. A new study shows that somatic activation of telomerase reverse transcriptase protein, an enzyme that maintains telomere length, ameliorates Alzheimer’s-disease-related phenotypes in mouse models and neurons derived from human induced pluripotent stem cells.

In this Review, the authors discuss the concept of molecular damage in aging, from theoretical models to experimental approaches and how to test interventions targeting aging that reduce its burden.

In the era of big data, looking for insights in large datasets has become the norm — and health data are no exception. Combining systems-biology-driven, endophenotype-based analysis of drug targets with large-scale medical claims data points to sildenafil as a potential treatment opportunity for Alzheimer’s disease.

Age-friendly cities initiatives aim to facilitate active and healthy aging. Focusing on the urban physical environment, the authors argue that longevity-ready cities that aim for better health and well-being for people of all ages from a life-course perspective can accomplish more than initiatives focused solely on old age.

Aging-related changes in DNA methylation have been used to estimate the biological age of organisms and tissues. Measuring DNA methylation in single cells is notoriously difficult and current methods only yield sparse methylation profiles, but a new computational method now offers the capability of profiling biological age at single-cell resolution.

Exposure to young blood slows down aging of several organs and prevents physical, cognitive and immune decline. However, how circulating factors mediate these effects is poorly understood. In this issue of Nature Aging, Sahu et al.¹ describe a key role for circulating extracellular vesicles in regulating skeletal muscle regeneration during aging, through the shuttling of Klotho transcripts.

The fact that women’s reproductive lifespans are finite affects many personal decisions and is accompanied by postmenopausal side effects. Expansion of the reproductive lifespan could therefore have many benefits. Findings from Zhang and colleagues indicate that manipulation of BIN2 extends the reproductive lifespan of female mice, and hold promise for therapeutic development.

What makes some human brains more resilient to aging than others? In an Article in Nature Aging, Chan et al. provide evidence that brain connectomes in older adults are altered by a college education — an environmental factor that might be an advantageous modulator of brain reserve during aging.

This Review provides an evidence-based update of the prevention and management of sarcopenia and proposes practical information to facilitate the disease’s adoption into routine care.

A new study provides broad evidence that older people are more generous than their younger counterparts, but that they favor local over global giving. In light of population aging and the relative wealth controlled by older citizens, it is important to identify the factors that contribute to these differences.

The apolipoprotein E gene ε4 allele (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). Over 60% of patients have at least one APOE4 allele. A drug discovery approach targeting aging and AD transcriptomic signatures suggests bumetanide might prevent or treat AD in people with the APOE4/APOE4 genotype.

This Review summarizes current research on cellular senescence including its molecular basis and examines how drugs may be targeted against senescent cells to treat age-related multimorbidities.

The ability to remain true to cellular identity and function is lost during aging and carcinogenesis when DNA damage triggers inflammation that progressively erodes homeostatic cues. Shalabi et al. show that these losses are accelerated in patients with germline cancer mutations in DNA repair genes and are independent of chronological age.

COVID-19 causes high mortality in older adults compared to younger people. Bartleson et al. review the immunological mechanisms that make older adults vulnerable to COVID-19 and discuss ways to bolster immunity in this population during COVID-19.

New research reveals that the mitochondrial citrate carrier is crucial for the accumulation of acetyl-CoA in the cytosol and nucleus, and efficient histone acetylation. Lysosomal degradation of this carrier drives mesenchymal stem cell aging in a process characterized by tightly packed chromatin and reduced expression of osteogenic genes.

The integrated stress response governs adaptive reprogramming of protein synthesis following external or internal signals. The authors discuss its role in aging and longevity, and highlight strategies to enhance health and resilience.

A new study shows that increased microRNA-31 expression is associated with hair follicle aging. Genetic deletion of the microRNA or pharmacological inhibition of its downstream effectors suppresses hair follicle stem cell aging in mice.

This Review synthesizes recent research on the mechanisms and roles of autophagy in health, aging and disease and discusses how drugs that modulate the process of autophagy could be used to suppress age-associated diseases.

Rockwood and colleagues discuss how measuring the degree of frailty helps us understand how aging gives rise to the diseases of aging, and aids translation from comprehensive geriatric assessment and individual care plans to geroscience and back.