Reviews & Analysis

Under conditions of stress, autophagic degradation of nuclear and nucleolar components was found to promot.e youthfulness and delay aging by preserving nuclear architecture and preventing nucleolar expansion, in somatic cells. We also found that nuclear-material autophagy serves as an essential quality-control mechanism that contributes to sustaining germline immortally.

We found that aging is accompanied by a reduction in cardiomyocyte nuclear size and increased stiffness, dependent on loss of A-type lamins. Mechanistically, age-dependent nuclear remodeling represses expression of cardiogenic transcription factors that are required for heart contractility. Preserving lamin or transcription factors delays cardiac decline.

We used data from the Longitudinal Aging Study in India (LASI) to provide up-to-date epidemiological estimates of the prevalence of vision impairment among the Indian population. We find that older adults, and particularly women, marginalized groups and those from lower socioeconomic strata, had a higher prevalence of visual impairment.

Our longitudinal study comparing the skin, gut and oral microbiomes of community-dwelling older adults and nursing home residents showed striking changes known to be linked to antibiotic resistance and disease risk. Such shifts were associated with frailty, not chronological age, and were most pronounced in the skin, the primary reservoir for infection risk.

Deep learning was applied to cellular images to predict senescence on the basis of nuclear morphology. These methods recognize senescence in diverse cell types, show increasing senescence with age in liver and dermis, and suggest that higher rates of senescence associate with several age-related diseases but reduced cancer risk.

Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in single cardiomyocytes from individuals across the human lifespan. Aged cardiomyocytes were found to have a higher burden of sSNVs and show mutational signatures that suggest failed repair of oxidative DNA damage.

Global measures of the rate of aging can identify individuals who age faster than average and are at increased risk of adverse outcomes. Combining information on multiple physiological measures collected over time generated a global measure of aging that strongly predicted changes in physical and cognitive function.

Epigenetic clocks based on DNA methylation are widely used aging biomarkers, but their utility is limited by technical noise. A method based on principal component analysis produces high-reliability clocks for applications such as longitudinal studies and intervention trials.

Older adults from long-term care facilities who had been infected with COVID-19 during the first wave of the pandemic were found to have robust cellular and humoral responses to SARS-CoV-2 spike protein. Importantly, serostatus did not affect humoral immunity to influenza or other respiratory syncytial viruses.

High-affinity tau-PET was used to apply the Braak neuropathological staging system for Alzheimer’s disease in vivo. Tau-PET can be used to stage Alzheimer’s disease from presymptomatic to clinical dementia phases in people, while also providing a framework to model the natural history of Alzheimer’s disease using biomarkers.

Forkhead box protein M1 (FOXM1) is a transcription factor with pleiotropic roles in cell proliferation, differentiation and senescence. This study shows that cyclic induction of a FOXM1 transgene in mouse models of Hutchison–Gilford progeria and natural aging significantly extends healthspan and ameliorates the senescence-associated histopathology driven by repression of endogenous Foxm1.

Mass spectrometry analysis of mouse cerebrospinal fluid revealed that several proteins change in abundance or structure during aging. The six proteins that show the most robust structural changes are associated with cognition or Alzheimer’s disease in human cerebrospinal fluid, thus revealing candidate diagnostic biomarkers and potential therapeutic targets.

In a sample of >19,000 older adults, the presence of depressive symptoms was associated with adverse medical outcomes over five years, including persistent physical disability, cancer and major bleeding episodes. Certain depression trajectories were associated with distinct health conditions. Systematic assessment of depressive symptoms may facilitate early identification of at-risk populations.

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.

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.