Reviews & Analysis

Older adults are at high risk of suffering debilitating health effects from COVID-19. Effective communication of associated risks is therefore paramount. A new study finds that imagining a personalized disease transmission event amplifies perceived risk and bolsters risk-related information seeking in older age.

Cellular senescence and smooth muscle cells are key features of the atherosclerotic plaque; however, how senescent cells regulate smooth muscle cells is largely unknown. Herein, a new study in Nature Aging illuminates this interplay, providing insights into plaque dynamics and stability with potentially profound implications for heart attack and stroke.

Inflammation is known to be elevated with progressive age. In this issue, Sayed et al. identify a group of circulating cytokines that correlate with health decline in aging, particularly the chemokine CXCL9. The findings offer a new understanding of how wellbeing and biological resilience are independent from chronological age.

Nursing home residents account for 41% of all COVID-19 deaths. Understanding why this occurs and the interplay between infectious agent, person, nursing home environment and operations, and public health responses is essential for families and governments when making decisions to protect loved ones and citizens, respectively.

The first longevity revolution led to lifespan extension. The next revolution will extend healthspan through the development of aging therapeutics. A new study describes the economic impact of success and how these interventions will work by analysing various scenarios labeled after characters from popular literature.

Arthur et al. leverage different types of big data, either generated in house from cohorts of healthy aging and COVID-19, or downloaded from the ever-increasing public data archives, to disentangle the distinct cellular and proteomic mechanisms of COVID-19 and aging.

A phase 2 clinical trial of active immunization against a pathological form of the tau protein provides evidence for feasibility of this approach. Although active treatment did not show benefits on clinical outcome measures, analyses of fluid biomarkers and of a subset of patients with predicted pathology provide hints of efficacy.

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ)-induced phosphorylation of the axon-stabilizing tau protein, which causes neurodegeneration. Here, Morshed et al. show that deregulated phosphorylation in AD also affects other proteins and cell types in the brain, suggesting that the tau-centric view on Aβ toxicity should be revised.

This Perspective discusses the socioeconomic concept of the longevity dividend, in which healthy and productive aging is achieved through a positive correlation between three dimensions: life expectancy, health and the economy.

Chronic inflammation, or ‘inflammaging’, is a key process in age-related diseases, and identification of the molecular players involved is a top priority. Cai and Han identified an evolutionary conserved functional lncRNA able to modulate the release of inflammatory SASP molecules from senescent cells through the NF-κB pathway.

This Review discusses evidence linking age-related hearing loss to depression and presents a model for the underlying neurobiological pathways, offering direction for future research to reduce risk for depression for older adults with impaired hearing.

The tumor microenvironment (TME) impacts different phases of tumor progression and therapy resistance. Zhang et al. show that senescent stromal cells activate an epigenetic program that controls the senescence-associated secretory phenotype and can be targeted to boost responses to chemotherapy.

Long-term exposure to air pollution is harmful to human health, causing damage to respiratory and cardiovascular systems. A new study provides evidence that even short-term, relatively low-level air pollution can be detrimental for cognitive function, and suggests the possibility that a commonly used drug might help reduce the harmful effects.

Using mouse models of osteoarthritis (OA), a new study finds that osteoclasts secrete exosomes that deliver miRNAs to chondrocytes, leading to an increase in metalloproteinase activity in cartilage. A bone-specific inhibitor of exosome production can halt this process, hinting at a new therapeutic strategy for patients with OA.

Groh and colleagues investigate the age-related degeneration of axons in the optic nerve and other brain regions and show that at least part of this degeneration is due to the presence of T cells.

In this Perspective, McMahon et al. examine the emerging roles and implications of post-transcriptional RNA modifications, or the epitranscriptome, in aging and age-related diseases, highlighting potential epitranscriptomic mechanisms and/or their dysfunction that may regulate the aging process.

Polypharmacy is a leading health concern entangled with many geriatric syndromes. This Review provides an overview of the current research landscape and a critical appraisal of existing and emerging approaches to address polypharmacy.

Chronological age fails to capture how the process of aging differs between individuals. Variability in rates of biological aging in youth is related to anatomical and functional differences already visible by midlife. This portends substantially different aging outcomes that have individual- and societal-level implications.

Biomarkers for Parkinson’s disease are critical to our efforts to identify disease-modifying therapies. Kern et al. document potential microRNA (miRNA) biomarkers and trends in miRNA regulation that occur in a bimodal distribution with age.

Zhang et al. describe a neural circuit that reduces lifespan when food-restricted worms smell food. This circuit signals the intestine via octopamine, the invertebrate homolog of norepinephrine, to activate AMPKα. Importantly, norepinephrine signaling also activates AMPKα in mammalian cells, suggesting a conserved mechanism.