1. Temperature

The life span of C. elegans is influenced by temperature. For example, Klass (1977) found that the mean life span of C. elegans cultured in liquid media was 23 days at 16°C, but 9 days at 25°C. One might assume that the different rates of growth at different temperatures are a direct consequence of the intrinsic thermodynamic properties of chemical reaction rates. However, Wong et al. (1995) found that mutants defective in clk (clock) genes are unable to adjust their rate of growth to changes in temperature. Wild-type animals actively decrease or increase their rate of development in response to temperature changes. In contrast, clk mutants cultured to the two-cell stage at 15°C or 25°C and then shifted to 20°C were unable to either increase or decrease their rate of development effectively. Thus, the clk genes are required to reset the rate of development in response to changes in temperature. This is a provocative finding, and it will be interesting to learn its molecular basis. These mutants also have altered life spans, as discussed below.

2. Food

3. Reproduction

The most straightforward way of determining whether progeny production influences life span is to sterilize animals and measure their life spans. This has been done in several ways. First, the life spans of worms unable to make sperm have been examined and found to be similar to those of wild type. These include fer-15 mutants, which produce defective sperm (Klass 1983; Friedman and Johnson 1988a), and fem mutants, which produce oocytes instead of sperm (Kenyon et al. 1993). In addition, life span is not affected by ablation of the gonad and germ cells (Kenyon et al. 1993). Therefore, in C. elegans, the production of progeny per se does not affect life span.

One sterile mutant, spe-26 , has been reported to have an extended life span (Van Voorhies 1992); however, in this case, the effect on life span is probably unrelated to the sperm defect, since the magnitude of the life-span extension in these mutants is not correlated with the degree of sterility in different spe-26 alleles (S. Ward, pers. comm.).

Does the act of mating itself affect life span? It appears that it does but it is not clear how. Van Voorhies (1992) found that mating decreased the life span of males. In fact, male life span appears to be shortened by mating, or attempted mating, with either males or hermaphrodites. When males are grown singly, their life spans are increased, an effect not seen with hermaphrodites (D. Gems and D.L. Riddle, pers. comm.). In the case of hermaphrodites, Van Voorhies (1992) found that mating did not affect the life span. However, in a subsequent, more extensive study, mating with males was found to reduce hermaphrodite life span by up to one half (Gems and Riddle 1996). The act of copulation itself seems to decrease life span, because sterile males that attempt to copulate also accelerate the death of hermaphrodites.

4. Oxygen Levels

Changes in oxygen concentration perturb the life span of C. elegans (Honda et al. 1993). When animals are cultured in a high concentration of oxygen, their life spans are shortened, and when they are cultured in a low concentration of oxygen, their life spans are lengthened. Furthermore, a strain with reduced levels of superoxide dismutase was more sensitive to the effects of oxygen. These findings suggest that oxidative damage can accelerate the aging process in C. elegans and argue that in nature, oxygen levels have a role in setting the normal life span.

5. DNA Damage

Hartman et al. (1988) questioned whether the effectiveness of DNA repair systems might determine the life expectancy of C. elegans. To address this issue, they asked whether there was a correlation between life span and sensitivity to three different DNA-damaging agents in recombinant inbred strains (described below) whose mean life spans range from 13 to 30 days. They found that there was no such correlation. This finding argues that the efficacy of DNA repair is not a limiting factor in determining the life span of wild-type C. elegans.

6. Relationship between Programmed Cell Death and Senescence

Mutations in ced genes, which alter programmed cell death, do not affect life span (R. Horvitz, pers. comm.). It thus seems likely that the regulation of programmed cell death (apoptosis) is fundamentally different from the process of organismal senescence and aging.