Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan

Abstract

Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation in shuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this “carry-over” effect might be the result of transcription regulation in embryos.

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

“…Of note, the only esg mutation associated with an increased life span was in a slightly different genetic background compared with the mutations associated with decreased life span, which indicate unknown epistatic interactions (Magwire et al, 2010 ). This evidence agrees with our data showing that the mutations in shuttle craft had different effects on life span in different genetic backgrounds (Pasyukova et al, 2004 ; Roshina et al, 2014 ) and the data from other researchers. For example, naturally segregating genes interact epistatically with Sod , a well-known aging gene, to modify its ability to extend longevity (Spencer et al, 2003 ).…”

“…Sex-specific and sex-antagonistic effects on life span are not rare (Tricoire et al, 2009 ; Ruiz et al, 2011 ; Roshina et al, 2014 ; Schriner et al, 2014 ; Shaposhnikov et al, 2015 ); for example, of 59 mutations increasing life span, 70.7% affected males and females differently (Magwire et al, 2010 ). In the initial screens and in our first experiment (Magwire et al, 2010 ), the effects of esg BG01042 on the life span of female flies were not statistically significant leading to the conclusion that esg BG01042 affects life span in a male-specific manner.…”

“…Life span was measured as described by Roshina et al ( 2014 ). To measure the life span of unmated flies, 5 virgin flies of the same genotype and sex, all collected on the same day from cultures with moderate density, were placed in replicate vials.…”

“…Locomotion was measured as described by Roshina et al ( 2014 ). Flies were collected and maintained by the same procedures as for the life span assays but without recording the deaths.…”

“…We have already demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in neural development affect life span in Drosophila melanogaster (Pasyukova et al, 2004 ; Rybina and Pasyukova, 2010 ; Roshina et al, 2014 ; Rybina et al, 2017 ). Among other genes, escargot ( esg ) was identified as a candidate gene affecting life span in a screen of more than 1,500 insertion mutations and the insertion located downstream of esg was further confirmed to be causally associated with life span control (Magwire et al, 2010 ).…”