C. elegans males look to be intrinsically longer-lived than hermaphrodites. A range of unc mutations extend male but not hermaphrodite lifespan, apparently by inhibiting some lifespan-reducing elements of wild-type male behaviour (1). The greater longevity of males requires
daf-16 (+), but appears independent of
daf-2 : previous studies showed that
daf-2 mutant males remain longer-lived than
daf-2 hermaphrodites (1). Conditional alleles of
daf-2 fall into two classes. In class 1 mutant hermaphrodites [e.g.
daf-2(
m41) ] the larval arrest phenotype is fully suppressed by
daf-12(
m20), while in class 2 mutant hermaphrodites [e.g.
daf-2(
e1370) ] it is not. Furthermore, in class 2 mutants, the
daf-2 extended lifespan is increased by
daf-12, while in class 1 mutants it is either unaffected or partially suppressed (e.g.
m41 )(2,3). We examined the effect of
daf-2-
daf-12 interactions on male lifespan, in monoxenic liquid culture (on plates a high proportion of males climb up the walls and die from desiccation). In
daf-2 mutants, lifespan increases in both sexes were mostly similar to those seen previously on plates. One exception was as follows: while
daf-2(
e1370) males were much longer-lived than hermaphrodites, as previously seen (1),
daf-2(
m41) males and hermaphrodites lifespans were identical.
daf-2 ;
daf-12 hermaphrodite lifespans were comparable to previous work (2,3). Surprisingly, the presence of
daf-12(
m20) had no effect on male lifespan, in either
daf-2(
e1370) or
daf-2(
m41) males (22.5oC). We also examined the effect of
daf-12 on male lifespan, either alone or in combination with
unc-32(
e189) , which blocks male mating behaviour and increases lifespan by ~60% (1). While a slight increase in median (but not maximum) male lifespan resulted from
daf-12 (+20%, p <0.01), compared with a reduction in hermaphrodite lifespan, (-10%, p <0.01), no effect on male lifespan was seen in the presence of
unc-32 . Thus, while
daf-12 plays an important role in hermaphrodite ageing (as shown by mutant interactions with
daf-2 and its requirement for lifespan extension resulting from germline ablation (4)), it appears to play no role in male ageing.
daf-12 encodes a nuclear hormone receptor (5), which is a candidate gene for the ultimate receipt and transduction of cell subset-specific signals from the insulin-like signalling pathway to control dauer formation and ageing (5). Our findings reveal sex-specific differences in genetic pathways regulating lifespan, and suggest the possibility that
daf-12 may not be expressed in adult males. (1) Gems, D. & Riddle, D.L. (2000) Genetics 154 : 1597-1610. (2) Larsen, P.L. et al. (1995) Genetics 139 : 1567-1583. (3) Gems, D. et al . (1998) Genetics 150 : 129-155. (4) Hsin, H. & Kenyon, C. (1999) Nature 399 : 362-366. (5) Antebi, A. et al. (2000) Genes & Dev 14 : 1512-1527.