Meta-analysis of DNA methylation aging signatures in 17 human tissues
Abstract Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD + metabolism, supporting NAD + as a potential therapeutic target in aging. A gene encoding a cell-adhesion protein, PCDHGA1, emerged as a conserved hub across tissues, implicating cell-to-cell communication pathways in aging across multiple organs. Our methylation atlas therefore provides a resource for dissecting the molecular basis of human aging and for identifying potential biomarkers and translational therapies.
Authors
- Steve Horvath (ORCID: https://orcid.org/0000-0002-4110-3589)
- Cassandra Malecki (ORCID: https://orcid.org/0000-0002-2367-9541)
- Matthew Taper (ORCID: https://orcid.org/0000-0002-3148-1615)
- Séverine Lamon (ORCID: https://orcid.org/0000-0002-3271-6551)
- James R. Broatch (ORCID: https://orcid.org/0000-0002-0082-3168)
- Macsue Jacques (ORCID: https://orcid.org/0000-0002-4337-7022)
- Vadim N. Gladyshev (ORCID: https://orcid.org/0000-0002-0372-7016)
- Navabeh Zarekookandeh (ORCID: https://orcid.org/0000-0002-5500-7328)
- Itamar Levinger (ORCID: https://orcid.org/0000-0001-9194-2033)
- Robin Grolaux (ORCID: https://orcid.org/0000-0001-5129-7308)
- Mahdi Moqri (ORCID: https://orcid.org/0000-0001-6675-0566)
- Elina Sillanpää (ORCID: https://orcid.org/0000-0001-6375-959X)
- C S Smith (ORCID: https://orcid.org/0000-0003-2677-9991)
- Mandhri Abeysooriya (ORCID: https://orcid.org/0000-0003-2163-6203)
- Jesse R. Poganik (ORCID: https://orcid.org/0000-0003-3098-8550)
- Andrew E. Teschendorff (ORCID: https://orcid.org/0000-0001-7410-6527)
- Miina Ollikainen (ORCID: https://orcid.org/0000-0003-3661-7400)
- Ida Blom (ORCID: https://orcid.org/0000-0003-1602-3031)
- Sean Lal (ORCID: https://orcid.org/0000-0002-5841-560X)
- Linn Gillberg (ORCID: https://orcid.org/0000-0003-0588-1663)
- Bernadette Jones (ORCID: https://orcid.org/0000-0003-4613-7865)
- Carlie Bauer (ORCID: https://orcid.org/0000-0002-6860-587X)
- Aino Heikkinen (ORCID: https://orcid.org/0000-0001-5770-6475)
- Kirsten Seale
- Bernadette Jones-Freeman
- Nathalie Saurat
- Adam P. Sharples
- Anna Lysenko
- Sarah Voisin
Institutions
- Edith Cowan University (AU)
- University of Copenhagen (DK)
- Brigham and Women's Hospital (US)
- University of Helsinki (FI)
- Harvard University (US)
- Deakin University (AU)
- The University of Western Australia (AU)
- Novo Nordisk (Denmark) (DK)
- Royal Prince Alfred Hospital (AU)
- Australian Regenerative Medicine Institute (AU)
- Shanghai Institute of Nutrition and Health (CN)
- Minerva Foundation (FI)
- Australian Institute for Musculoskeletal Science (AU)
- Institute for Molecular Medicine Finland (FI)
- Central Finland Health Care District (FI)
- Baird Institute (AU)
- Monash University (AU)
- Victoria University (AU)
- Norwegian School of Sport Sciences (NO)
- University of Jyväskylä (FI)
Publication Details
- Journal
- Nature Aging
- Published
- 2026-06-26
- DOI
- https://doi.org/10.1038/s43587-026-01164-5
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Heart Foundation of Australia
- National Natural Science Foundation of China
- Academy of Finland
- Norges Forskningsråd
- Australian Research Council
- National Health and Medical Research Council