Longevity—the ability to maintain health and function across an extended lifespan—is determined by an intricate interplay between genetic architecture and epigenetic regulation. Breakthrough discoveries have identified numerous genes and molecular pathways, from DNA repair and metabolic control to immune function and stress resistance, that shape variation in lifespan and healthspan among individuals and across species. At the same time, it’s increasingly clear that epigenetic mechanisms—such as DNA methylation, histone modification, and regulatory non-coding RNAs—modulate how genes respond to environmental factors, influencing the trajectory of aging.

Despite substantial advances, important questions remain: Which genetic and epigenetic signatures most powerfully predict longevity? How do inherited factors interact with modifiable environmental cues? Can targeted interventions shift epigenetic marks to promote healthy aging or reduce the burden of age-related diseases?

For this Research Topic, we invite all article types—including original research, reviews, systematic reviews and meta-analyses, methods, mini-reviews, case reports, data reports, hypotheses, perspectives, and opinion pieces—on all aspects of the genetic and epigenetic determinants of longevity. Suitable themes and approaches include, but are not limited to:

1. Discovery and functional analysis of longevity-associated genes in humans or model organisms
2. GWAS, multi-omics, and systems biology studies revealing pathways that govern lifespan
3. Epigenetic modifications and remodeling in aging tissues
4. Development and application of biological age clocks and other biomarkers
5. Interactions between genetic or epigenetic factors and lifestyle/environmental exposures
6.Transgenerational epigenetic inheritance and its effect on aging
7. Therapeutic or preventive approaches targeting genetic/epigenetic mechanisms to extend healthspan

By bringing together diverse insights and research methods, this collection aims to advance understanding of how genetics and epigenetics shape the course of aging, highlight innovative methodologies and interventions, and stimulate collaboration within the geroscience community. We especially encourage submissions that bridge basic and translational research and that suggest actionable targets for promoting healthy longevity.

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Genetic and Epigenetic Determinants of Longevity