The Free Radical/Oxidative Damage Theory (Harman, 1956 J. Gerontol. 11,.
p298) is generally regarded as the most plausible explanation for aging.. It implies that reactive oxygen species (ROS), inevitable by-products of. oxidative metabolism, are the primary cause of molecular damage to cells,. and consequently of aging. Because ROS are mainly produced by. mitochondria, these organelles are in the spotlights of recent aging. research.. In C. elegans, lifespan is regulated in part by the insulin/IGF-1 pathway.. Reduction of Ins/IGF-1 (IIS) signaling via mutation in the
daf-2 gene,. which encodes an insulin/IGF-1-like receptor, not only increases lifespan,. but also enhances stress resistance and alters metabolism. While effects. of reduced Ins/IGF-1 signaling on lifespan and stress resistance are clear-. cut, its consequences on metabolism are not (Braeckman et al, 2002 Aging. Cell 1,
p82). If metabolism is measured as oxygen consumption rate, then. there is little difference in metabolic rate between wild type and the long-. lived mutant. Yet mutation in
daf-2 decreases heat production, which is a. measure for total catabolic activity. The combination of both parameters. as the caloric-to-respirometric ratio hints at an increased catabolic. efficiency in
daf-2, which may implicate alterations in mitochondrial. oxidative phosphorylation, and consequently, in ROS production. In this. study, we aim to elucidate the balance between metabolism, mitochondrial. function, ROS production, ROS defense and ROS damage in the long-lived C.. elegans strain
daf-2(
e1370).. Our data suggest that isolated mitochondria from
daf-2(
e1370) are capable. of maintaining their mitochondrial function and efficiency at old age.. This may imply a higher proton motive force; indeed, higher ROS production. rates were found compared to mitochondria from aged wild type. Higher ROS. production is likely to be overcompensated by the enhanced stress defense. of
daf-2; this may explain the lower oxidative damage found in the long-. lived mutant.. Whole worm assays show that
daf-2(
e1370) metabolism is shifted towards a. higher efficiency, generating less heat and more ATP for the same amount of. oxygen consumed.. Seemingly, mitochondrial efficiency reflects whole worm oxidative. metabolism. However, metabolic differences between WT and
daf-2 may not. be exclusively explained by differences in mitochondrial coupling. In. addition to mitochondrial function, crosstalk between the nucleus and the. mitochondria likely influences metabolic efficiency.