title: Acute stress response modified by modest inhibition of growth hormone axis: a potential machinery of the anti-aging effect of calorie restriction.
abstract: Calorie restriction (CR) may exert antiaging effects by inhibiting the growth hormone (GH)/IGF-1 axis. The present study investigated the effect of modest inhibition of GH signaling on stress response and compared it with the effect of CR. Heterozygous (tg/-) rats of a transgenic strain of male rats, whose GH signaling was inhibited by overexpression of the anti-sense GH gene, and wild-type (WT) rats were used. Rats were fed ad libitum (AL) or 30% CR diets from 6 weeks of age. At 6 months of age, rats were killed between 0 and 8h after lipopolysaccharide (LPS) injection to evaluate the acute phase stress response. tg/- rats had less tissue injury, indicated by blood aspartate aminotransferase (AST) concentrations, than WT rats. Successive waves of incremental plasma TNF-α, IL-6, and interferon (IFN)-γ levels were also attenuated in tg/- rats. Activation of NF-κB, a redox-sensitive transcription factor, was slightly diminished in tg/- rats, whereas the AP-1 activity was increased. Similar trends were also observed in the CR groups as compared to the AL groups. The present results suggest an involvement of the GH/IGF-1 axis in the effect of CR for stress response, even if CR does not act solely through the GH axis.
authors.affiliation: Department of Investigative Pathology, Unit of Basic Medical Science, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Trindade
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Henmi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ushiroda
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D016207:Cytokines / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I