Metabolic Signatures of Life Span Regulated by Mating, Sex Peptide, and Mifepristone/RU486 in Female Drosophila melanogaster.
Animals
Animals, Genetically Modified
Caenorhabditis elegans
/ drug effects
Drosophila Proteins
/ genetics
Drosophila melanogaster
/ drug effects
Ecdysone
/ metabolism
Female
Gene Expression Regulation
/ drug effects
Genes, Insect
Hormone Antagonists
/ pharmacology
Intercellular Signaling Peptides and Proteins
/ genetics
Juvenile Hormones
/ metabolism
Longevity
/ drug effects
Male
Methoprene
/ pharmacology
Mifepristone
/ pharmacology
Sexual Behavior, Animal
/ physiology
Signal Transduction
/ drug effects
1/3-methylhistidine
Aging
Juvenile hormone
Kynurenine pathway
Urate
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
18 01 2021
18 01 2021
Historique:
received:
23
12
2019
pubmed:
11
7
2020
medline:
15
7
2021
entrez:
11
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32648907
pii: 5865319
doi: 10.1093/gerona/glaa164
pmc: PMC7812429
doi:
Substances chimiques
Drosophila Proteins
0
Hormone Antagonists
0
Intercellular Signaling Peptides and Proteins
0
Juvenile Hormones
0
male accessory gland peptide, Drosophila
0
Mifepristone
320T6RNW1F
Ecdysone
3604-87-3
Methoprene
8B830OJ2UX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-204Subventions
Organisme : NIA NIH HHS
ID : R01 AG063371
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG001751
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057741
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013280
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG049494
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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