Figure 1

Levels of 12 A heteroplasmy at 5172 in the origin of light strand replication negatively correlate to lifespan in mice. (a) Next generation sequencing of blood DNA obtained from moribund B6 and B6-mt^AKR (AKR) mice shows that AKR exhibits significantly higher levels of the 12 A heteroplasmy at 5172 in the origin of light strand replication (OriL) compared with B6 (***P = 0.003, ****P < 0.0001; two-way ANOVA). (b) The higher levels of 12 A heteroplasmy in OriL are observed in different tissues (liver, brain and heart). The difference becomes more prominent when mice are aged (17–22 months old). *P < 0.05, multiple t-test. (c) The heteroplasmy at 5172 is also detected in wild house mice (Mus musculus domesticus) caught on farms (n = 215). (d–f) Survival curve of B6 and B6-mt^AKR (AKR) in both sexes (d), males (e), and females (f). Female AKR display a significantly shorter lifespan compared with B6 (P = 0.0305, log-rank test). (g) The higher 12 A heteroplasmy levels in OriL correlate with the shorter lifespan (ρ = −0.1881 P = 0.0235, Spearman test).