McCulloch, Diana; (2003) Sex differences in ageing in the nematode Caenorhabditis elegans. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Males of the nematode Caenorhabditis elegans are longer-lived, more stress resistant and more likely to enter an alternative dispersal stage (dauer) than hermaphrodites. Why might this be? Since these traits are suppressed by insulin-/IGF-l-like signalling (IIS), it seemed possible that IIS levels could be lower in males. Increased male lifespan and stress resistance were dependent upon daf-16, which encodes the transcription factor negatively regulated by IIS, suggesting that IIS is down-regulated in males. Moreover, the male bias to dauer formation was lost in IIS mutants. However, DAF-16::GFP was more localised to the nucleus (where it is active) in hermaphrodites, hence sex differences in DAF-16 activity may occur downstream of IIS. Lifespan is extended by certain uncoordinated (unc) mutations, which disrupt motility by affecting neurons or musculature. Only neuronal unc mutations extended lifespan, suggesting that disruption of neurotransmission and/or neuroendocrine function may be responsible. The 76-dependence of the lifespan increase due to several unc mutations suggests that IIS may be the component affected. Since unc mutations increase lifespan more in males than hermaphrodites, sex differences in IIS/ DAF-16 activity may underlie this effect, at least in part. Hermaphrodite lifespan is regulated by gonadal signalling. Lifespan responses of males to ablation of gonad precursors were reduced relative to hermaphrodites, suggesting reduced lifespan regulation by the male gonad. Moreover, in contrast to hermaphrodites, male lifespan was largely unaffected by mutation of daf-12, which encodes a nuclear hormone receptor that interacts with IIS and is involved with transduction of gonadal signals. Overall, therefore, evidence suggests fundamental sex differences in lifespan regulation. Why might this evolve? Studies of several dioecious and other androdioecious species suggested that increased male lifespan is a general trait among nematodes. Potentially, differential degrees of male rarity and exposure to non-senescent modes of death shape evolution of sex differences in lifespan.

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