title: Growth hormone signaling is necessary for lifespan extension by dietary methionine.
abstract: Growth hormone significantly impacts lifespan in mammals. Mouse longevity is extended when growth hormone (GH) signaling is interrupted but markedly shortened with high-plasma hormone levels. Methionine metabolism is enhanced in growth hormone deficiency, for example, in the Ames dwarf, but suppressed in GH transgenic mice. Methionine intake affects also lifespan, and thus, GH mutant mice and respective wild-type littermates were fed 0.16%, 0.43%, or 1.3% methionine to evaluate the interaction between hormone status and methionine. All wild-type and GH transgenic mice lived longer when fed 0.16% methionine but not when fed higher levels. In contrast, animals without growth hormone signaling due to hormone deficiency or resistance did not respond to altered levels of methionine in terms of lifespan, body weight, or food consumption. Taken together, our results suggest that the presence of growth hormone is necessary to sense dietary methionine changes, thus strongly linking growth and lifespan to amino acid availability.
authors.affiliation: Department of Basic Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, 58203, USA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Brown-Borg
authors.forename: Sharlene G
authors.initials: SG
authors.lastname: Rakoczy
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Wonderlich
authors.forename: Lalida
authors.initials: L
authors.lastname: Rojanathammanee
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: Vanessa
authors.initials: V
authors.lastname: Armstrong
authors.forename: Debbie
authors.initials: D
authors.lastname: Raasakka
mesh_terms: D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008715:Methionine / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction
chemical_list: D013006:Growth Hormone; D008715:Methionine
keywords: dwarf; growth hormone; lifespan; methionine; mice