Biomaterial Database

Metabolic Signatures of Life Span Regulated by Mating, Sex Peptide, and Mifepristone/RU486 in Female Drosophila melanogaster. 2021

Gary N Landis, and Devon V Doherty, and Chia-An Yen, and Lu Wang, and Yang Fan, and Ina Wang, and Jonah Vroegop, and Tianyi Wang, and Jimmy Wu, and Palak Patel, and Shinwoo Lee, and Mina Abdelmesieh, and Jie Shen, and Daniel E L Promislow, and Sean P Curran, and John Tower

Molecular and Computational Biology Section, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles.

Mating and transfer of male sex peptide (SP), or transgenic expression of SP, causes inflammation and decreased life span in female Drosophila. Mifepristone rescues these effects, yielding dramatic increases in life span. Here targeted metabolomics data were integrated with further analysis of extant transcriptomic data. Each of 7 genes positively correlated with life span were expressed in the brain or eye and involved regulation of gene expression and signaling. Genes negatively correlated with life span were preferentially expressed in midgut and involved protein degradation, amino acid metabolism, and immune response. Across all conditions, life span was positively correlated with muscle breakdown product 1/3-methylhistidine and purine breakdown product urate, and negatively correlated with tryptophan breakdown product kynurenic acid, suggesting a SP-induced shift from somatic maintenance/turnover pathways to the costly production of energy and lipids from dietary amino acids. Some limited overlap was observed between genes regulated by mifepristone and genes known to be regulated by ecdysone; however, mifepristone was unable to compete with ecdysone for activation of an ecdysone-responsive transgenic reporter. In contrast, genes regulated by mifepristone were highly enriched for genes regulated by juvenile hormone (JH), and mifepristone rescued the negative effect of JH analog methoprene on life span in adult virgin females. The data indicate that mifepristone increases life span and decreases inflammation in mated females by antagonizing JH signaling downstream of male SP. Finally, mifepristone increased life span of mated, but not unmated, Caenorhabditis elegans, in 2 of 3 trials, suggesting possible evolutionary conservation of mifepristone mechanisms.

UI	MeSH Term	Description	Entries
D007605	Juvenile Hormones	Compounds, either natural or synthetic, which block development of the growing insect.	Insect Growth Regulator,Insect Growth Regulators,Juvenile Hormone,Growth Regulators, Insect,Regulators, Insect Growth,Growth Regulator, Insect,Hormone, Juvenile,Hormones, Juvenile,Regulator, Insect Growth
D008136	Longevity	The normal length of time of an organism's life.	Length of Life,Life Span,Lifespan,Life Spans,Lifespans
D008297	Male		Males
D008726	Methoprene	Juvenile hormone analog and insect growth regulator used to control insects by disrupting metamorphosis. Has been effective in controlling mosquito larvae.	Altosid,Altosid PS-10,ZR-515,Altosid PS 10,Altosid PS10,ZR 515,ZR515
D004331	Drosophila melanogaster	A species of fruit fly frequently used in genetics because of the large size of its chromosomes.	D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D004440	Ecdysone	A steroid hormone that regulates the processes of MOLTING or ecdysis in insects.	Molting Hormone
D005260	Female		Females
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006727	Hormone Antagonists	Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.	Antagonists, Hormone
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia