Sex‐specific regulation of aging in Caenorhabditis elegans

Abstract

SummaryA fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3–7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites—which are essentially females capable of sperm production—over males is established by TRA‐1, the terminal effector of the sex‐determination pathway. This transcription factor directly controls the expression of daf‐16/FOXO, which functions as a major target of insulin/IGF‐1 signaling (IIS) and key modulator of aging across diverse animal phyla. TRA‐1 extends hermaphrodite lifespan through promoting daf‐16 activity. Furthermore, TRA‐1 also influences reproductive growth in a DAF‐16‐dependent manner. Thus, the sex‐determination machinery is an important regulator of IIS in this organism. These findings provide a mechanistic insight into how longevity and development are specified unequally in the two genders. As TRA‐1 is orthologous to mammalian GLI (glioma‐associated) proteins, a similar sex‐specific mechanism may also operate in humans to determine lifespan.

The sex- and duration-dependent effects of intermittent fasting on lifespan and reproduction of spider mite Tetranychus urticae

“…Understanding the physiological difference associated with gene expression variation between sexes maybe crucial for understanding the mechanism of sex-specific aging. Additionally, another study with C. elegans indicated that the longevity advantage of hermaphrodites over males was influenced by the terminal transcription factor (TRA-1) of the nematode sex-determination pathway, which can activate the expression of daf-16/ FOXO to regulate development and lifespan [44]. However, whether the protein TRA-1 is evolutionary conserved and functions in other species warrants further investigation.…”

Aging attenuates redox adaptive homeostasis and proteostasis in female mice exposed to traffic-derived nanoparticles (‘vehicular smog’)

“…A highly relevant aspect of the present study is the exploration of sex-dependent differences in a mammalian model. Earlier studies have demonstrated a clear sexual dimorphism in stress protective responses and activation of the adaptive response in lower organisms [49, 50]. Moreover, sex is a strong predictor of lifespan in mammals, with females typically outliving males [51, 52].…”

Sex-specific regulation of neuronal functions in Caenorhabditis elegans: the sex-determining protein TRA-1 represses goa-1/Gα(i/o)

“…Until now, TRA-1 was known to determine sexual fates by primarily regulating the activity of intermediate regulatory genes like egl-1 and ceh-30 (cell death), mab-3 and lin-39 (transcription), fog-3 (translation), xol-1 (sex-determination), daf-16 (ageing) and unc-6 (Conradt and Horvitz 1999;Yi et al 2000;Chen and Ellis 2000;Schwartz and Horvitz 2007;Mason et al 2008;Hargitai et al 2009;Szabó et al 2009;Berkseth et al 2013;Hotzi et al 2018;Weinberg et al 2018). Some of these target genes shape the physical structure of the nervous system itself.…”

“…TRA-1 specifies hermaphrodite fates by repressing male-specific genes. Its target genes identified so far include egl-1 (egg-laying defective; it controls sexually dimorphic cell deaths), mab-3 (male abnormal; it governs male development and behaviour), fog-3 (feminization of germline; it determines germ cell fate), ceh-30 (C. elegans homeobox; it protects malespecific neurons from undergoing apoptosis), dmd-3 (doublesex/mab-3 domain family; it regulates sex-specific morphogenesis), xol-1 (XO lethal; the master sex-switch gene), lin-39 (abnormal cell lineage; it controls vulval development), daf-16 (dauer larva formation defective; it is required for longevity and dauer larva development) and unc-6 (uncoordinated; it affects synaptic connectivity) (Conradt and Horvitz 1999;Yi et al 2000;Chen and Ellis 2000;Schwartz and Horvitz 2007;Mason et al 2008;Hargitai et al 2009;Szabó et al 2009;Berkseth et al 2013;Hotzi et al 2018;Weinberg et al 2018). In this study, we identified a novel TRA-1 target gene, goa-1.…”