Fig. 2: Age accumulation of mitochondrial mutations across body sites.
From: Mitochondrial clonal mosaicism encodes a biphasic molecular clock of aging
a, The number of tissue-private mutations (somatic mutations found only in a single tissue sample) per individual across 15 representative tissues, stratified by age group. The average number for the remaining tissues within each germ layer origin (endoderm, mesoderm and ectoderm) is also presented. The stacked bars at the bottom illustrate the number of mutations shared across multiple tissues within an individual, categorized by the number of germ layers in which they occur (1, 2 or all 3). b, Mitochondrial mutations and clonal expansion with age in the liver. The number of mutations represents the average across individuals within each age group. Total heteroplasmy reflects the summation of the heteroplasmy of all variants in an individual. Linear regression shows a significant increase in mutation count with age (β = 0.31 mutations per year, P = 4 × 10−16, n = 190 individuals). c, The rate of mutation accumulation (β, mutations per year) assessed by linear regression across six representative tissues. The shaded areas represent the 95% confidence interval (CI) for the linear regression line β. d, Differential rates (β) of age-related mutation accumulation across all tissues, derived from linear regression (sample sizes per tissue indicated in d). The error bars represent the 95% CI, which is based on the t-statistic of the corresponding mutation rate β and total heteroplasmy μ estimates. The asterisks indicate significant age-dependent mutation rate β (P < 0.001, FDR <0.05 after Bonferroni correction). Sample sizes (n, number of individuals) are marked on top of β estimates of each tissue. Detailed statistics for each tissue are provided in Supplementary Table 2. Tissues in this panel are color-coded to represent different tissue types, following the standard GTEx conventions (Extended Data Fig. 2). e, The relationship between age-related mutation accumulation (mutations per 10 years) with the total number of somatic mutations and their total heteroplasmy at an advanced age (60 years old), with the circle size representing the total heteroplasmy of somatic mutations. In b and d, box plots display the median (center line), interquartile range (IQR, box limits) and whiskers (extending to 1.5× IQR); notches indicate 95% CI for the median.
