Worm Breeder's Gazette 17(2): 40 (April 1, 2002)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Department of Biology, University College London, Gower Street, London WC1E 6BT U.K.
When maintained in isolation to prevent attempted mating, N2 males live ~20% longer than hermaphrodites (1). Solitary male but not hermaphrodite lifespan is further enhanced by a range of uncoordinated (unc) mutations. It was first proposed that this was because these mutations prevented life-shortening behaviour, even in solitary males (1). We have since found, however, that the male unc lifespan effect is limited to neuronal unc mutations and is not seen in muscle uncs (10 mutants tested, data not shown). Thus, many defects affecting the nervous system retard ageing in males but not hermaphrodites.
One possibility is that this reflects sex differences in the neuroendocrine regulation of ageing. Dauer formation is regulated by interacting genetic pathways, involving insulin/IGF signalling (IIS) and TGF-beta signalling, with a parallel and/or regulatory cGMP component. Dauer constitutive (Daf-c) mutations in the IIS pathway increase adult lifespan, while those in the TGF-beta/ cGMP pathways do not. Wild-type males form dauers more readily than hermaphrodites in response to dauer pheromone (2), as do several Daf-c mutants (3). Could it be that wild-type males are both longer-lived and more likely to form dauers than hermaphrodites because IIS is constitutively reduced in males? We investigated whether (a) the male bias to dauer formation and (b) the intrinsic male longevity were dependent on IIS. For this we looked at dauer formation and lifespan ratios of the two sexes in a range of IIS, TGF-beta and cGMP mutants.
(a) Dauer formation: Progeny from mated hermaphrodites were raised at a temperature that gave a mix of dauers and non-dauers. The sex of non-dauers and recovered dauers was scored, and the overall ratio of male: hermaphrodite dauer formation was determined (Table).
Strain | Temp (oC) | MH dauer ratio | N* | Strain | Temp (oC) | MH dauer ratio | N* |
N2 | 25 | 1.20 | 309 (1) | daf-4(m592)b | 22.5 | 2.60 | 2453 (3) |
daf-2(m41)a | 20 | 0.82 | 2486 (3) | daf-1(m40)b | 22.5 | 4.89 | 469 (1) |
daf-2(e1370) a | 22.5 | 1.04 | 1116 (2) | daf-8(m85)b | 17 | 9.53 | 1031 (1) |
daf-2(e1365) a | 22.5 | 0.48 | 2644 (2) | daf-11(m47)c | 15 | 1.67 | 209 (1) |
daf-2(e1368) a | 22.5 | 0.49 | 4421 (2) | daf-16(mgDf50); daf-1(m40)ab | 22.5 | 3.26 | 3596 (2) |
pdk-1(sn709) a | 26 | 0.66 | 858 (2) |
* Number of worms scored (number of trials); aIIS mutant; bTGF-beta mutant; ccGMP/ TGF-beta mutant
There was a marked male bias to dauer formation in wild type, as previously seen (2), as well as in the TGF-beta and cGMP mutants. However, either no bias or a hermaphrodite bias was observed in IIS mutants. This indicates that the increased tendency of males towards dauer formation is dependent on IIS. However, when partial dauer formation was measured in a daf-16; daf-1 double mutant, the male bias as seen in dauer formation by the daf-1 single mutant was only slightly reduced. This implies that a complex interplay of IIS and TGF-beta signalling may be involved.
(b) Survival analysis: When lifespan was measured under identical conditions (monoxenic liquid culture) for daf-2 and daf-16 mutants, the increased N2 male longevity was no longer apparent, with hermaphrodites living slightly longer than males (data not shown). The increased male longevity still remained in pdk-1(sn709), however. These results suggest that increased male longevity is dependent on daf-2 signalling via daf-16, but that this might not act via pdk-1.
Altogether, these results are consistent with a constitutive reduction of IIS in males, leading to increased dauer formation and longevity.
(1) Gems, D, Riddle, DL (2000) Genetics 154: 1597. (2) Ailion, M, Thomas, JH (2000) Genetics 156: 1047. (3) Vowels, JJ, Thomas, JH (1992) Genetics 130: 105.