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

Jacques M, Seale K, Voisin S, Lysenko A, Poganik JR, Moqri M, Gladyshev VN, Horvath S, Teschendorff A, Eynon N

1. 01

   Aging produces both conserved and tissue-specific epigenetic signatures across 17 human tissues

2. 02

   Systemic shifts in methylation level, increased methylation variability and growing molecular disorder with age

3. 03

   Network analysis identified tightly connected gene clusters NOT modified by beneficial interventions

4. 04

   A separate, more modifiable cluster was linked to NAD+ metabolism, supporting NAD+ as a candidate therapeutic node

5. 05

   PCDHGA1, encoding a cell-adhesion protein, emerged as a conserved cross-tissue aging hub

Study Design

Meta-Analysis

Sample Size

15,000 subjects

Study Duration

Cross-sectional meta-analysis

Methodology

Meta-analysis of >15,000 publicly available and newly generated human DNA methylation profiles spanning 17 tissues, with network/module analysis of age-associated CpGs and cross-referencing against intervention-responsive genes.

Limitations

Descriptive and network-level, not interventional. The NAD+ association identifies a methylation module that appears modifiable in principle; it is NOT evidence that NAD+ precursor supplementation improves human aging outcomes. Tissue representation is uneven across the 17 tissues and largely cross-sectional.