Table 2.
Epigenetic clocks in animal models.
| Study | Animal Model | DNA Methylation Analysis | Intervention | Biological Matrix/Tissue | Number of CpG Sites | Impact of Diet or CR |
|---|---|---|---|---|---|---|
| Maegawa et al. 2017 [25] | Mice and Rhesus macaques | DREAM Methylation analysis [106] |
Mice: 40% CR starting at 0.3 years of age until 2.7–3.2-year-old. Rhesus macaques: 30% CR starting in middle age (age: 7–14 y) and analyzed at 22–30 years of age (CR treatment period: 15–21 years). |
Blood | 24 | Animals under CR had significantly lower epigenetic predicted ages compared to their chronological age. |
| Wang et al. 2017 [46] | Female mice (UM-HET3 mice) |
RRBS | 60% CR until 22-months-old | Liver | 148 | Reduction of epigenetic age of 9.4 months on average in CR mice versus their age-matched controls. |
| Stubbs et al. 2017 [100] | Male mice (C57BL/6J) |
RRBS | Low-fat–high-carbohydrate diet or high-fat–low carbohydrate diet | Multi-tissue predictor applied to liver samples [107] | 329 | Animals on high-fat diet showed accelerated epigenetic aging. |
| Petkovich et al. 2017 [103] | Male mice (C57BL/6J and B6D2F1) |
RRBS | Dietary intervention started at 14 weeks for all mice, until 10, 18, 23, or 27 months (C57BL/6J mice) or until 21 or 27 months (B6D2F1 mice). | Multi-tissue | 90 | On average, mice under CR had an epigenetic age 20% lower than their chronological age. The effect was less pronounced in younger animals than in older ones. |
| Thompson et al. 2018 [102] | Mice (use of publicly available datasets) |
RRBS [103] and WGBS [42] |
WT UM-HET3 mice: CR diet initiated at 4 months of age until 22 months of age [42]. C57BL/6 and B6D2F1 mice: see above Petkovich et al. [103] |
Multi-tissue | Development of four new models of epigenetic clock (elastic net clock, ridge regression clock, two conserved clocks) | Delayed epigenetic aging effects observed in C57BL/6, B6D2F1, and HET3 mice under CR. |
| Meer et al. 2018 [101] | Male mice (C57BL/6J and B6D2F1) |
RRBS | C57BL/6 and B6D2F1 mice: see above Petkovich et al. [103] | Multi-tissue | 435 | Shift towards a younger age in animals under CR, but difference not statistically significant. |
RRBS: reduced-representation bisulfite sequencing; WGBS: whole-genome bisulfite sequencing.