in hermaphrodites (Fig. 2B, fig. S2A, and table S2).
Genes whose expression was increased in re-
sponse to males were enriched for insulin sig-
naling (P = 4.3 × 10−3) [e.g., insulin peptides
(ins-4, ins-11, ins-23, and ins-31), which are
expressed in neurons], transthyretin-related fam-
ily members (P = 4.3 × 10−3) [which are involved
in neurodegenerative diseases in mammals
(8)], and G protein–coupled chemoreceptors
(P = 1.9 × 10−3) (which are expressed in sensory
neurons) (fig. S2B). In contrast, genes whose ex-
pression was decreased in response to males were
Fig. 2. Male-induced changes in gene expression in hermaphrodites and attenuation of male-induced demise in ins-11 mutants. (A) Schematic
of the microarray design. (B) Unbiased clustering of
the genes whose mRNAs show increased (red) (341)
or decreased (blue) (289) abundance in hermaphrodites in response to males (three independent
experiments). (C) RNAi to ins-11 specifically ameliorates the male-induced shortening of life span in
hermaphrodites from a strain that is sensitized for
neuronal RNAi (log rank P < 0.0001). (D) RNAi to
F11A5.3 reduces the male-induced shortening of life
span in hermaphrodites from a strain that is sensitized
for neuronal RNAi (log rank P < 0.0001). (E) RNAi to
utx-1 reduces the male-induced shortening of life
span in hermaphrodites from a strain that is sensitized for neuronal RNAi (log rank P < 0.0001). (F)
ins-11(tm1053) hermaphrodite mutants exhibit partial
protection from the demise induced by wild-type males
(log rank P < 0.0001), although they are able to successfully mate. Statistics are included in table S1.
Fig. 3. Role of diffusible substances secreted
by males in shortening the life span of hermaphrodites. (A) Schematic for male-conditioned plates.
(B) Shortened life span of wild-type hermaphrodites
exposed to secreted substances from males [log rank
P < 0.0001 when plates were conditioned with 30
males/plate or 150 males/plate (5X)]. (C) che-13(e1805)
hermaphrodites are resistant to male-induced shortening of life span (fig. S3, A and B) (log rank P <
0.5038). (D) daf-22(m130) males do not shorten
the life span of wild-type hermaphrodites, as well
as wild-type males (fig. S3, A and B) (statistically
significant difference by log rank, P < 0.0001). (E)
daf-22(m130) males do not shorten the life span of
daf-2(e1370) hermaphrodites, as well as wild-type
males (statistically significant difference by log rank,
P < 0.0001). (F) Medium conditioned by daf-22(m130)
males does not significantly shorten the life span of
wild-type hermaphrodites (log rank P = 0.9177).
Statistics are included in table S1.