Meta-analysis of DNA methylation aging signatures in 17 human tissues.

Macsue Jacques, Kirsten Seale, Sarah Voisin, Anna Lysenko, Robin Grolaux, Bernadette Jones-Freeman, Severine Lamon, Mandhri Abeysooriya, Itamar Levinger, Carlie Bauer, Adam P Sharples, Aino Heikkinen, Elina Sillanpaa, Miina Ollikainen, Cassandra Smith, James R Broatch, Navabeh Zarekookandeh, Linn Gillberg, Ida Blom, Jesse R Poganik, Mahdi Moqri, Vadim N Gladyshev, Matthew Taper, Cassandra Malecki, Sean Lal, Nathalie Saurat, Steve Horvath, Andrew Teschendorff, Nir Eynon

Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia.Australian Regenerative Medicine Institute, Monash University, Melbourne, Victoria, Australia. · pubmed

Paper

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

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Research summary

This meta-analysis identifies conserved and tissue-specific DNA methylation patterns associated with aging across 17 human tissues, providing a foundational map of epigenetic drift but offering no direct mechanism for intervention or lifespan extension. The study characterizes the phenomenon of epigenetic aging rather than solving its root causes or demonstrating how to reverse it, representing an incremental descriptive advance in the field of geroscience.

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