Abstract
BackgroundSexual differentiation often has significant effects on life span and aging phenotypes. For example, males and females of several species have different life spans, and genetic and environmental manipulations that affect life span often have different magnitude of effect in males versus females. Moreover, the presence of a differentiated germ-line has been shown to affect life span in several species, including Drosophila and C. elegans.MethodsExperiments were conducted to determine how alterations in sexual differentiation gene activity might affect the life span of Drosophila melanogaster. Drosophila females heterozygous for the tudor[1] mutation produce normal offspring, while their homozygous sisters produce offspring that lack a germ line. To identify additional sexual differentiation genes that might affect life span, the conditional transgenic system Geneswitch was employed, whereby feeding adult flies or developing larvae the drug RU486 causes the over-expression of selected UAS-transgenes.ResultsIn this study germ-line ablation caused by the maternal tudor[1] mutation was examined in a long-lived genetic background, and was found to increase life span in males but not in females, consistent with previous reports. Fitting the data to a Gompertz-Makeham model indicated that the maternal tudor[1] mutation increases the life span of male progeny by decreasing age-independent mortality. The Geneswitch system was used to screen through several UAS-type and EP-type P element mutations in genes that regulate sexual differentiation, to determine if additional sex-specific effects on life span would be obtained. Conditional over-expression of transformer female isoform (traF) during development produced male adults with inhibited sexual differentiation, however this caused no significant change in life span. Over-expression of doublesex female isoform (dsxF) during development was lethal to males, and produced a limited number of female escapers, whereas over-expression of dsxF specifically in adults greatly reduced both male and female life span. Similarly, over-expression of fruitless male isoform A (fru-MA) during development was lethal to both males and females, whereas over-expression of fru-MA in adults greatly reduced both male and female life span.ConclusionManipulation of sexual differentiation gene expression specifically in the adult, after morphological sexual differentiation is complete, was still able to affect life span. In addition, by manipulating gene expression during development, it was possible to significantly alter morphological sexual differentiation without a significant effect on adult life span. The data demonstrate that manipulation of sexual differentiation pathway genes either during development or in adults can affect adult life span.
Highlights
Sexual differentiation often has significant effects on life span and aging phenotypes
For the germ lineablated male flies the mean and median life span was increased by +19.9% and +12.9%, respectively, relative to controls, whereas in contrast female life span was significantly decreased (Table 2)
While the initial experiment indicated a decrease in the life span of germ line-ablated females relative to controls, this result was not reproduced in the larger cohorts, where there was no significant difference in any of the mortality rate parameters between germ line-ablated females and controls
Summary
Sexual differentiation often has significant effects on life span and aging phenotypes. The disposable soma theory suggests that aging occurs because there is a selection pressure to assign limited biological resources to short-term survival, growth, and reproduction, rather than long-term survival [1,2]. Consistent with this idea, several studies have suggested that there may exist a trade-off between reproduction and life span. In C. elegans, elimination of reproduction by ablation of the germ line extended life span by up to +60% [6] This effect was attributed to increased activity of the insulin/IGF1-like signaling (IIS) pathway target transcription factor DAF-16 in the gastrointestinal tract, caused by reduced hormonal signaling from the gonad to the intestine [7]. One possibility is that it is sexual differentiation, rather than reproduction per se, that exerts a cost on life span [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
