Editors' ChoiceAging

Male pheromones and high temperature reduce life span

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Sci. Signal.  01 Nov 2016:
Vol. 9, Issue 452, pp. ec257
DOI: 10.1126/scisignal.aal2962

Caenorhabditis elegans is widely used as a model organism for studying aging and life span. C. elegans populations consist primarily of self-fertilizing hermaphrodites together with a few males. One of the factors that influence the life span of these nematodes is the germline: C. elegans hermaphrodites that lack a germ line live longer than do intact hermaphrodites. Another factor that influences the life span of hermaphrodites is the presence of males: Male pheromones shorten the life span of hermaphrodites regardless of whether mating occurs or the hermaphrodite has a germ line. Aprison and Ruvinsky found that, even though male-specific mixtures of ascaroside pheromones accelerated hermaphrodite aging, they increased fertility and delayed germline senescence. C. elegans hermaphrodites can make only enough sperm to support reproduction for a few days. After that, egg production largely ceases until the worms mate. When hermaphrodites were aged on plates that had previously held males or in the presence of male-specific mixtures of ascarosides, upon mating they produced more offsprings and had more germline progenitor cells than hermaphrodites aged in the absence of male pheromones. The authors also found that some other factor produced by males accelerated the development of hermaphrodites. Young hermaphrodite larvae reared on plates previously inhabited by wild-type males or males that could not make ascarosides reach sexual maturity faster than did hermaphrodites aged on plates previously inhabited only by hermaphrodites. Genetic experiments suggested that the responsible factor was likely to be one or more steroids. Thus, male pheromones prompt hermaphrodites to shunt more resources into the germ line at the expense of somatic tissues. Commentary from Maklakov and Friberg discusses reproductive strategies for balancing the allocation of resources between the germ line and soma.

High temperature also promotes aging and reduces life span. The thermosensory AFD neurons protect C. elegans from the life span–shortening effects of high temperature by promoting the synthesis of steroid hormones. Chen et al. found that the ability of AFD neurons to mitigate the negative effect of high temperature on life span required phosphorylation of the cyclic AMP–responsive element binding protein (CREB) homolog CRH-1 by the calmodulin-dependent kinase I homolog CMK-1 in these neurons. High temperature stimulated the transcription of flp-6 and the secretion of the FMRFamide neuropeptide that this gene encodes in a manner that depended on CRH-1 and the CRE of the flp-6 promoter. Overexpressing flp-6 or crh-1 extended the life span of worms under high-temperature conditions, and expressing flp-6 specifically in AFD neurons rescued the shortened life span of flp-6 and crh-1 mutants. Genetic experiments placed crh-1 and flp-6 upstream of steroid signaling, as expected, but transcriptomic analysis indicated that flp-6 also repressed the expression of genes involved in insulin signaling. Indeed, flp-6 reduced the expression of ins-7, which encodes an insulin-like peptide that shortens life span, in intestinal cells. Thus, the neuropeptide FLP-6 is important for the ability of a C. elegans thermosensory circuit to compensate for the deleterious effect of high temperature on life span (see also Artan et al.).

E. Z. Aprison, I. Ruvinsky, Sexually antagonistic male signals manipulate germline and soma of C. elegans hermaphrodites. Curr. Biol. 26, 2827–2833 (2016). [PubMed]

A. A. Maklakov, U. Friberg, Ageing: Why males curtail the longevity of their mates. Curr. Biol. 26, R929–R932 (2016). [PubMed]

Y.-C. Chen, H.-J. Chen, W.-C. Tseng, J.-M. Hsu, T.-T. Huang, C.-H. Chen, C.-L. Pan, A C. elegans thermosensory circuit regulates longevity through crh-1/CREB-dependent flp-6 neuropeptide signaling. Dev. Cell 39, 209–223 (2016). [PubMed]

M. Artan, S. W. A. An, S.-J. V. Lee, Heat FLiPs a hormonal switch for longevity. Dev. Cell 39, 133–134 (2016). [PubMed]