As originally described, the
clk-1 mutants of C. elegans develop slowly and exhibit an extended life span. Recently, the
clk-1 mutants have been shown to have a defect in the biosynthesis of coenzyme Q 9 , the normal isoform synthesized by C. elegans where 9 designates the number of isoprene units in the polyisoprenoid tail. Coenzyme Q is an essential component of the mitochondrial respiratory electron transport chain, as it is required for the function of complexes I, II, and III. The
clk-1 mutants lack coenzyme Q 9 and instead rely on the coenzyme Q 8 supplied by their standard diet of E. coli . These results implied that a reduction in the levels of coenzyme Q may be responsible for the slowed development and increased life span reported for the
clk-1 mutants maintained on the standard Q-replete E. coli diet. Wild type worms appear to partially rely on dietary Q, as evidenced by a one-day delay in development (egg to adult) on Q-less food. To test whether a decrease in coenzyme Q could alter life span of wild type animals, wild-type L4 larvae were switched from a standard diet of Q 8 -replete E. coli to a diet lacking coenzyme Q, and were subsequently maintained on this Q-less diet throughout adulthood. Three distinct E. coli mutant strains were provided as Q-less diets, including strains lacking either the O - or C -methyltransferase enzymes of Q biosynthesis, and an E. coli mutant lacking the 4-HB:polyprenyldiphosphate transferase. A 60% increase in nematode life span was observed for the first two of these Q-less E. coli strains, suggesting that the distinct Q-biosynthetic intermediate accumulating in each of these Q-less E. coli mutants was not responsible for producing the observed life span extension. Thus at face value, consumption of Q 8 shortens wild type life span and it is this short life span that is considered normal. Alternatively, the diet/environment interaction that changes longevity could be due to different metabolic products in the Q-replete and Q-less bacteria. Mutations in two loci,
daf-12 and
daf-16 , suppress the life span extension of a number of previously isolated Age mutations. However, neither
daf-12 nor
daf-16 suppress the life span extension generated by the Q-less E. coli diet. Assuming that the life span extension resulting from the Q-less E. coli diet is a phenocopy of the
clk-1 mutation, then the lack of suppression by
daf-16 is consistent with previous reports. The Age mutants
clk-1(
qm30,
qm51, and
e2519 ) and
daf-2(
e1370 and
m41 ) at the restrictive temperature, were transferred to the Q-less E. coli diet as L4 larvae, and for each of the mutants tested, further increases in life span were observed. For
clk-1 mutants, the expectation had been premature death, since its larval development depends on a supply of dietary Q. However, it is likely that the
clk-1 mutants cultured on Q-replete E. coli during development accumulate coenzyme Q 8 , and the life span extension observed for the adult animals is presumably due to the declining levels of Q 8 from lack of a dietary source. The increased life span extension in Age mutants fed diets lacking coenzyme Q suggest that these longevity mechanisms are additive.