News & Views

Transcription factors can control cell identity and function in health and disease. However, how they do so during aging is incompletely explored. Maity and colleagues identify age-related changes in gene regulation by analyzing the expression patterns of transcription-factor target genes in single-cell transcriptomics data.

Compromised clearance of dysfunctional mitochondria, through the process of mitophagy, has garnered attention as an essential contributor to aging and neurodegeneration. Schmid and colleagues¹ reveal that genetic enhancement of mitophagy via neuronal overexpression of BNIP3 alleviates brain aging and prolongs healthspan in fruit flies.

Tau neuropathology is a defining feature of Alzheimer’s disease. For decades, its progression throughout the cortex has been captured post mortem using Braak stages. A new study replicated Braak staging in living patients using positron emission tomography, showing associations with other biomarkers and clinical deficits.

Aging is accompanied by a gradual decline of cell proliferation potential. FOXM1 is a transcription factor involved in cellular proliferation and cell cycle progression. Ribeiro et al. show that cyclic expression of a truncated form of a FOXM1 transgene in vivo can delay senescence-associated progeroid and natural aging phenotypes in mice.

Public health policies recommend maintaining a body mass index below 25, after which individuals are considered to be overweight or obese. A new study looked at optimal BMI in adults in China in their ninth decade or older, and concludes that these recommendations need to be revised upwards in this age group.

Neurodegenerative diseases, including Parkinson’s disease, are linked to the accumulation of defective mitochondria in the brain and to microbial dysbiosis in the gut. However, the interplay between these factors is incompletely understood. Fedele et al. reveal how gut mitochondrial dysfunction activates intestinal inflammation to drive neurodegeneration in a Parkinson’s disease model.

Frailty is an important age-related prognostic for mortality, and little is known about its immune landscape. Luo et al.¹ use single-cell profiling to gather a comprehensive understanding of immune changes that happen from birth to old age, and provide new insights into the often-overlooked state of frailty.

Apolipoprotein E (APOE) is an important regulator of lipid metabolism and is genetically associated with longevity and age-related diseases such as Alzheimer’s disease. However, the molecular mechanisms that link APOE and aging are incompletely understood. Now an article in Nature Aging reveals that nuclear APOE promotes senescence by destabilizing heterochromatin.

While investigating sex differences in T cell aging, Mkhikian et al. identified a role for excessive IL-7 signaling and N-glycan branching in age-related T cell dysfunction in women and female mice. These findings point to the increasingly recognized importance of the effects of biological sex on immune aging, and delineate new targetable pathways in age-related immune dysfunction.

In cohorts of young and older adults who were comprehensively phenotyped, Janssens and colleagues traverse an important translational gap by providing compelling evidence for the purported link between elevated NAD⁺ levels and the healthy aging muscle phenotype in humans.

In cultured cells and in mice with accelerated aging, brief bursts of Yamanaka reprogramming factors reverse some molecular and functional deficits of aging without inducing pluripotency or teratomas. Browder et al. show that partial reprogramming regimens rejuvenate some tissues of physiologically aged mice without overt safety concerns.

Vascular senescence has been implicated in atherosclerosis. By characterizing SNPs in the p16-encoding CDKN2A/B locus, a new study in Nature Aging identifies CUX1 as a binding protein of an atherosclerosis-associated functional SNP, which activates CDKN2A expression and senescence in endothelial cells, thus providing a mechanism of transcriptional senescence regulation.

Telomeres, the caps of chromosomes, shorten with age. Using qPCR, Nilhesh Samani, Veryan Codd and colleagues measured leukocyte telomere length in close to half a million individuals from the UK Biobank, confirming several previous associations. This dataset offers many new opportunities to explore associations between leukocyte telomere length and other traits relevant to human aging and health.

As the elderly population continues to grow exponentially, dry eye disease is becoming increasingly common. In this issue, Sasaki and colleagues identified a NAD⁺-regulated steroidogenic pathway in the eye that supports the normal function of meibomian glands, and show that increasing the availability of NAD⁺ can alleviate the dry eye phenotype of aged mice.

Countries are advancing retirement age as life expectancy advances. But increases in healthy life expectancy are not keeping pace with total life expectancy, lengthening the portion of life spent with disability and threatening the capacity of individuals to work longer. Now, a study forecasts healthy life expectancy for people in England in 2035.

Many aging-related traits share a common genetic component. How to disentangle it from trait-specific effects has remained largely unexplored. A new study in Nature Aging uses an analysis framework for isolating the shared genetic component in GWAS of aging-related traits, and identifies genomic loci that contribute to longevity.

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.