Identification of chemical compounds as an inhibitor of mitochondrial ATP synthesis, leading to an increased stress resistance and an extended lifespan in C. elegans

It is well known that the disruption of the mitochondrial respiratory components prolongs lifespan in many species. The mitochondrial stress response can lead to an increased survival rate through the restoration of the cellular homeostasis. Therefore, developing pharmacological interventions that induce mitochondrial stress response may be desirable to delay the onset of age-related diseases and promote a healthy life. In this study, we present chemical compounds, revealed by systematic screening of chemical libraries, which inhibit mitochondrial ATP synthesis in mammalian cells. Our study demonstrates that these compounds alter the body length and promote the oxidative stress response which leads to an increased longevity in Caenorhabditis elegans. Thus, our study identifies chemical compounds that may have potential therapeutic applications through affecting the mitochondrial function. •Our screen identifies inhibitors of mitochondrial ATP synthesis in HeLa cells.•Key respiratory components inhibited by chemical compounds are identified.•Chemical compounds affect ATP levels, stress resistance and lifespan in C. elegans.