Abstract
Tricarboxylic acid cycle (TCA cycle) is an essential metabolism pathway and plays an important role in extending lifespan. In this research, I studied the effect of isocitrate dehydrogenase A-1 (idha-1) expression upon RNAi knockdown on the lifespan in C. elegans. Here I found that RNAi knockdown of idha-1 shortens the lifespan and also decreases the oxidative stress tolerance in C. elegans. Both the NADPH+ and NAD+ concentrations in the idha-1 RNAi treated worms were down-regulated. Furthermore, the decreased oxygen consumption indicates that lower respiration rate and weaker energy production capability occur in the idha-1 RNAi knockdown worms. In addition, several aging related genes expression were altered upon idha-1 knockdown, like autophagy related genes: unc-51 and bec-1, lipase gene: lipl-4, ROS scavenger gene: sod-3, were down regulated in the idha-1 knockdown worms. I used STRING functional protein association networks found IDHA-1 can bind with IDHB-1 and IDHG-2. By RT-PCR, I found that knockdown of idha-1 also decreased the expression levels of idhb-1 and idhg-2, which both also reduce lifespan in C. elegans. Knockdown of idha-1, idhb-1, or idhg-2 reduces the extended lifespan of eat-2 mutant. Together, my thesis research indicated that idha-1 is required to maintain normal lifespan and uphold oxidative stress tolerance.