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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.
This Review provides an update on the pleiotropic effects of mitochondria in aging and discusses how defects in mitochondrial stress pathways contribute to the decline in cellular and systemic homeostasis during aging and age-related diseases.
Plant-based diets emphasizing healthful plant foods were associated with a lower risk of mortality among older adults, whereas a plant-based diet rich in less-healthful plant foods was related to a higher mortality risk. Thus, the quality of plant foods deserves attention in future plant-based dietary recommendations.
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.
Life expectancy is partially determined by an individual’s genetic make-up. Whole-exome sequencing analysis of >350,000 UK Biobank participants revealed that protein-truncating variants in four genes, BRCA1, BRCA2, ATM and TET2, are negatively associated with human lifespan. Phenome-wide analyses confirm roles for these genes in cancer and clonal hematopoiesis.
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.
Suicide is an important problem among older adults and in particular older men. Here, the author discusses factors that impact suicide risk, including social determinants of health and cultural perception of old age, and proposes strategies for a multifaceted approach to suicide prevention.
