It is well established that replicative life span in S. cerevisiae is enhanced by mitochondrial respiration. Recently, our group showed that increased respiratory rates in yeast result in lower mitochondrial reactive oxygen species (ROS) generation and enhanced chronological life span. Here, we studied yeast strains that express human superoxide dismutase (SOD) mutants that cause amiotrophic lateral sclerosis, a disease associated to changes in mitochondrial respiration and oxidative stress. We monitored S. cerevisiae chronological life using Fun^â1 metabolization and colonies counts, and found no changes in survival between wild-type strains and those expressing mutant SOD. O₂ consumption and ROS release in isolated mitochondria from these cells were also equal. These results suggest that SOD mutants that cause respiratory changes in human cells do not affect yeast mitochondria. As a second model in which chronological life span could be related to mitochondrial metabolism, we studied deltaNPT1 and deltaBNA6 cells in which NAD⁺ synthesis is impaired and replicative life span is affected. We found that these mutants present lower respiratory rates, increased ROS release and decreased chronological life span. Furthermore, caloric restriction increased respiration, decreased ROS and enhaced life span. Altogether, our results support the concept that enhanced chronological life span in S. cerevisiae is intimately linked to mitochondrial respiration and ROS release.

Supported by FAPESP and CNPq.