Natural variation for lifespan and stress response in the nematode Caenorhabditis remanei

Abstract

Genetic approaches (e.g. mutation, RNA interference) in model organisms, particularly the nematode Caenorhabditis elegans, have yielded a wealth of information on cellular processes that can influence lifespan. Although longevity mutants discovered in the lab are instructive of cellular physiology, lab studies might miss important genes that influence health and longevity in the wild. C. elegans has relatively low natural genetic variation and high levels of linkage disequilibrium, and thus is not optimal for studying natural variation in longevity. In contrast, its close relative C. remanei possesses very high levels of molecular genetic variation and low levels of linkage disequilibrium. To determine whether C. remanei may be a good model system for the study of natural genetic variation in aging, we evaluated levels of quantitative genetic variation for longevity and resistance to oxidative, heat and UV stress. Heritability (and the coefficient of additive genetic variation) was high for oxidative and heat stress resistance, low (but significant) for longevity, and essentially zero for UV stress response. Our results suggest that C. remanei may be a powerful system for studying natural genetic variation for longevity and oxidative and heat stress response, as well as an informative model for the study of functional relationships between longevity and stress response.

Figure 1. Differences in lifespan of C. remanei isofemale lines.

Top row: age-specific survival (S(t)) of females (A), males (B). Middle row: age-specific hazard (risk of death) of females (C), males (D) Hazard is defined as the instantaneous risk of death. Although hazards have no universal scale, max hazard (100% risk of death within the following day) for these data is one. The reciprocal of the hazard 1/h(t) is expected time to death, given survival to age t. Bottom row: mean adult lifespan of females (E) and males (F); bars are standard errors. Lifespan displayed low but significant heritability and coefficient of additive genetic variation (Table 1).

Figure 2. Mean survival of females from C.remanei isofemale lines after a 16 hour heat stress at 37.5°C.

Worms were exposed as one-day-old adult virgins. Heritability for heat stress resistance was high (h^{2  =}0.45, Table 1), and significantly greater than those for longevity or UV stress (Mann-Whitney U, P<0.0001).

Figure 3. C. remanei survival during exposure to 3.5 mM H₂O₂, plotted by sire.

(A) Age-specific survival (S(t)) and (B) age-specific hazard for males (dashed lines) and females (solid lines). Max hazard (100% risk of death within the next 30 minutes) for these data is 0.08. Control worms (housed in S basal only, not exposed to H₂O₂) experienced no death during the assay; mortality not shown. Heritabilities were high for females and males (h² = 0.95 and 0.75 respectively, Table 1) and were significantly greater than heritability for longevity or UV stress (Mann-Whitney U, P<0.0001).

Figure 4. Mortality rates (hazard) after exposure of C. remanei to 2000 J/m² UV, plotted by sire.

Dashed lines = males, solid lines = females. (A) Age-specific survival (S(t)); (B) Age-specific hazard. Max hazard (100% risk of death within the next 30 minutes) for these data is 1.0. Although there is a large sex effect on oxidative stress resistance, there is no evidence for significant variation among offspring of different sires (h ²∼0.00, Table 1).