Fig. 3: Applications of universal pan-mammalian clocks in human cohorts, reprogramming experiment and murine anti-aging studies.
From: Universal DNA methylation age across mammalian tissues
a,b, Forest plots representing the fixed effect (FE) model meta-analysis, combining HRs from Cox regression models for time to death, based on epigenetic age acceleration measures of clock 2 (AgeAccelClock2) and clock 3 (AgeAccelClock3) across different ethnic groups within two epidemiological cohorts. Each row indicates an HR for a 1-year increase in the age acceleration (AgeAccel) measure, along with a 95% confidence interval (CI). c,d, DNAmAge estimates of human dermal fibroblasts during OSKM-induced reprogramming. The y axes are DNAmAge estimates of clock 2 and clock 3 at day 0, 3, …, 42 and 49, respectively, during reprogramming31. e, Evaluations of mouse anti-age interventions: (1) age-matched Snell dwarf mutation study: 48 normal and 47 dwarf mice with ages of approximately 0.52 (mean ± s.d. = 0.52 ± 0.01) years, (2) age-matched whole-body GHRKO experiment 1 (Exp.1) with 36 normal and 35 GHRKO mice (mean ± s.d. = 0.65 ± 0.06 years), (3) age-matched GHRKO experiment 2 with GHRKO in livers only with 48 normal and 48 GHRKO genotypes (mean ± s.d. = 0.51 ± 0.03 years old), (4) Tet gene-KO study with all samples at age 0.5 years (Tet1, 32 controls and 32 Tet1 KO; Tet2, 33 controls and 32 Tet2 KO; Tet3, 31 controls and 32 Tet3 KO) and (5) CR study in livers (59 in CR versus 36 control mice with all ages at 1.57 years old). Comparisons in experiments 2 and 3 were based on AgeAccel measures. The color gradient is based on the sign of t-test for controls versus experimental mice, with a positive sign indicating that the mice in the control group exhibit higher age acceleration than the mice in the experimental group. f, Bar plots for selective tissue types and clocks across Snell dwarf mice (eight normal and eight dwarf mice) GHRKO experiment 1 (12 normal and 11 GHRKO mice), Tet3-KO mice (15 normal and 16 Tet3-KO mice) and the entire CR experiment, respectively. The orange dots in c and d and the blue dots in e correspond to individual observations. The y axes of the bar plots depict the mean of one standard error. All P values reported are two sided and are unadjusted for multiple testing.
