The authors found that, across tissues and in multiple datasets, aging is accompanied by a length-associated transcriptome imbalance. In most cases, a decrease in the relative abundance of long transcripts was observed and could be reversed by interventions targeting aging.

Somatic mutations accumulate with age; however, the role they have in cardiac aging is unclear. Here Choudhury et al. describe the somatic mutation landscape of human heart muscle cells by single-cell whole-genome sequencing and report mutational signatures indicative of increased oxidative DNA damage and failed repair.

Transcription factors control cell identity and function in health, disease and aging. Here the authors identify age-associated changes of transcriptional regulatory networks in single cells, revealing cell-type and tissue-type-independent patterns in key pathways, including circadian rhythm, antigen processing, collagen processing and inflammation.

Martínez Corrales et al. show that the activation of the conserved pro-longevity transcription factor FOXO solely in youth promotes subsequent health and survival in female fruit flies, via chromatin remodeling and induction of Xbp1.

Microglia, the innate immune cells of the brain, exhibit diverse functions and can influence Alzheimer’s disease progression. This study explores human microglial diversity in Alzheimer’s disease, uncovering unique disease-associated microglial populations and predicting underlying gene regulatory networks.

The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.

Oocyte meiotic defects increase with age and contribute to decreased oocyte quality. Here the authors show that granulosa cell mevalonate pathway abnormalities contribute to aneuploidy during ovarian aging and that supplementation with mevalonate metabolites improves oocyte quality, providing a potential therapeutic strategy for promoting female reproductive longevity.

Studies have identified sex and/or gender differences in Alzheimer’s disease, but few have examined other dementias. We highlight sex and gender differences in other dementias, discuss sociocultural factors and provide a framework for future global studies.

Rapid progress in the development of novel biomarkers and lifestyle interventions and the emergence of the first disease-modifying therapy have revolutionized our approach to dementia diagnosis, prevention and therapy. In this Focus issue, Nature Aging presents a collection of reviews and opinion pieces on recent advances in dementia research.

The World Health Organization (WHO) blueprint for dementia research provides a roadmap to addressing the challenges in the field and reshaping our approach to dementia research. This Comment focuses on how to operationalize the drivers of research highlighted in the blueprint to make research more equitable, impactful and global.