The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment |
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Authors: | Kathryn A. Kaiser Inga Kadish Thomas van Groen Daniel L. Smith Jr. Stephanie Dickinson Beate Henschel Erik S. Parker Andrew W. Brown David B. Allison |
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Affiliation: | 1. Department of Health Behavior, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA;2. Department of Cell, Developmental and Integrative Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA;3. Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham, Birmingham, Alabama, USA;4. Department of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, Indiana, USA;5. Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA |
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Abstract: | Interventions for animal lifespan extension like caloric restriction (CR) have identified physiologic and biochemical pathways related to hunger and energy-sensing status as possible contributors, but mechanisms have not been fully elucidated. Prior studies using ghrelin agonists show greater food intake but no effect on lifespan in rodent models. This experiment in male C57BL/6J mice tested the influence of ghrelin agonism for perceived hunger, in the absence of CR, on longevity. Mice aged 4 weeks were allowed to acclimate for 2 weeks prior to being assigned (N = 60/group). Prior to lights off daily (12:12 cycle), animals were fed a ghrelin agonist pill (LY444711; Eli Lilly) or a placebo control (Ctrl) until death. Treatment (GhrAg) animals were pair-fed daily based on the group mean food intake consumed by Ctrl (ad libitum feeding) the prior week. Results indicate an increased lifespan effect (log-rank p = 0.0032) for GhrAg versus placebo Ctrl, which weighed significantly more than GhrAg (adjusted for baseline weight). Further studies are needed to determine the full scope of effects of this ghrelin agonist, either directly via increased ghrelin receptor signaling or indirectly via other hypothalamic, systemic, or tissue-specific mechanisms. |
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Keywords: | aging ghrelin agonist lifespan mice |
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