By measuring the life spans of various recombinant inbreds, Johnson and Wood estimated that genetic variability accounted for 20% to 50% of C. elegans life span. 1 We measured life span of animals over two successive generations and found that, while some variation exists in from generation to generation, the life span of a parent had little effect on that of its progeny. What are the environmental factors that control the balance of life span? Studies with the
mev-1 gene provide evidence that reactive oxygen species (ROS) generated during respiration are key environmental factors in this process. Mev-1 mutants are hypersensitive to oxygen and methyl viologen (a singlet oxygen generator) and age precociously, particularly at high oxygen concentrations. 2 They also accumulate various aging markers more rapidly than does wild type. 3 The
mev-1 mutation is in the cytochrome b subunit of succinate dehydrogenase (
cyt-1 ), which compromises enzymatic activity of the mitochondrial complex II. 4 It is likely that, as a result of this mutation, significantly higher levels of ROS are generated during respiration. Mev-1 animals shown hypermutability to oxygen, which represents the first example of a mitochrondrial dysfunction impacting nuclear mutation frequencies. In addition, temperature affects life span differently in
mev-1 and wild type, likely through these metabolic differences. Electron microscopy reveals inclusions in the mitochondria of
mev-1 animals, particularly under elevated oxygen concentrations. In addition,
mev-1 embryos contain abnormally high numbers of
ced-3 -dependent apoptotic cells. Collectively these data muster substantial support for the theory that ROS-induced damage is important in biological aging. 1 Johnson and Wood 1982 PNAS 79, 6603 2 Ishii et al., 1990 Mutat. Res. 237, 165. 3 Hosokawa et al., 1994. MAD 74, 161; Adachi et al., 1998 J. Geront. 53A, B240 4 Ishii et al., 1998. Nature 394, 6694