News & Views in 2021

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 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.

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.

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.

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.

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.

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.

The gut microbiota controls immunity and brain function, but its role in cognitive aging is unclear. Boehme et al. found that fecal microbiota transplantation from young into aged mice attenuated cognitive impairments and reversed differences in hippocampal metabolites, and some aspects of peripheral and brain immunity.

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.