Figure 5. Specific antibiotics extend lifespan by phenocopying mrps-5 knockdown.

a, Effects on worm lifespan of doxycycline (30μg/mL), compared to carbenicilin (30μg/mL) or vehicle. p≤0.001 refers to statistical significance of doxycycline compared to either vehicle or the carbenicilin control. Antibiotics were given throughout life in panels a–e. b, The effects of doxycycline on lifespan are dose-dependent. c–e, Doxycycline induced UPR^mt (c, n=5) and reduced respiration (d, n=10), without changing citrate synthase activity (e, n=3). f–k, When treated only during larval development, doxycycline (6μg/mL; f–h) and chloramphenicol (100μg/mL; i–k) extend lifespan (f, i), induced UPR^mt (g, j, n=5) and reduced respiration (h, k, n=6). l, Doxycycline alters the ratio between nDNA- (ATP5A) and mtDNA-encoded (MTCO1) OXPHOS proteins in worms. m, Doxycycline decreased respiration in a cultured hepatocyte cell line (n=5), n, induced Hsp60 transcription, as measured using an Hsp60 promoter reporter (n=8), o, increased HSP60 protein expression and altered the ratio of nDNA- (UQCRC2) versus mtDNA- (MTCOI) encoded proteins (n=2). p, Doxycycline increased HSP60 protein and altered the ratio of nDNA- versus mtDNA-encoded proteins in primary murine hepatocytes. q, Doxycycline (50 mpkd) for 10 days in C57BL/6N mice decreased oxygen consumption (n=10). See also Supplementary Table 2.