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Meta-analysis of DNA methylation aging signatures in 17 human tissues
Macsue Jacques1, Kirsten Seale2,3, Sarah Voisin4
1Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.
Nature Aging
|June 26, 2026
Summary
Aging causes consistent epigenetic changes, like DNA methylation, across human tissues. These findings reveal conserved aging patterns and potential therapeutic targets for longevity.
Area of Science:
- Epigenetics and Molecular Biology
- Gerontology
- Genomics
Background:
- Epigenetic alterations, particularly DNA methylation, are hallmarks of aging.
- Understanding conserved patterns of epigenetic change across human tissues is crucial for aging research.
Purpose of the Study:
- To investigate conserved and tissue-specific DNA methylation patterns during human aging.
- To identify molecular pathways and potential therapeutic targets associated with aging.
Main Methods:
- Meta-analysis of over 15,000 human methylation profiles from 17 diverse tissues.
- Network analysis to identify gene clusters and key regulatory hubs involved in aging.
Main Results:
- Identified both conserved and tissue-specific epigenetic signatures of aging.
- Observed systemic shifts in methylation levels, increased variability, and molecular disorder with age.
- Discovered a modifiable gene cluster linked to NAD+ metabolism and identified PCDHGA1 as a conserved aging hub.
Conclusions:
- Aging induces consistent epigenetic modifications across human organs.
- NAD+ metabolism and cell-to-cell communication pathways are implicated in aging.
- The study provides a valuable resource for aging research, biomarker discovery, and therapeutic development.
