title: Assessment of mitochondrial biogenesis and mTORC1 signaling during chronic rapamycin feeding in male and female mice.
abstract: Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension in females than in males. Whether rapamycin treatment inhibits protein synthesis or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control or rapamycin-supplemented (Rap) diet for 12 weeks. Protein synthesis in mixed, cytosolic (cyto), and mitochondrial (mito) fractions and DNA synthesis and mTORC1 signaling were determined in skeletal muscle, heart, and liver. In both sexes, mito protein synthesis was maintained in skeletal muscle from Rap despite decreases in mixed and cyto fractions, DNA synthesis, and rpS6 phosphorylation. In the heart, no change in protein synthesis occurred despite the decreased DNA synthesis. In the heart and liver, Rap males were more sensitive to mTORC1 inhibition than Rap females. In conclusion, we show changes in protein synthesis and mTORC1 signaling that differ by sex and tissue.
authors: Department of Health and Exercise Science, Colorado State University, 220 Moby B Complex, Fort Collins, CO 80523-1582. benjamin.f.miller@colostate.edu.
authors: Joshua C
authors: JC
authors: Drake
authors: Frederick F
authors: FF
authors: Peelor
authors: Laurie M
authors: LM
authors: Biela
authors: Molly K
authors: MK
authors: Watkins
authors: Richard A
authors: RA
authors: Miller
authors: Karyn L
authors: KL
authors: Hamilton
authors: Benjamin F
authors: BF
authors: Miller
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology; D017666:Deuterium Oxide / Q000494:pharmacology; D004032:Diet / Q000379:methods; D005260:Female; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D063269:Mitochondrial Turnover / Q000187:drug effects*; D046912:Multiprotein Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D046912:Multiprotein Complexes; D038601:Ribosomal Protein S6; C448579:ribosomal protein S6, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D017666:Deuterium Oxide; D020123:Sirolimus
keywords: 2H2O; Deuterium; Mitochondria; Protein synthesis; Rapamycin; mTOR.
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