Children’s Nutrition Research Center Staff Publications

Language

English

Publication Date

4-1-2023

Journal

Aging Cell

DOI

10.1111/acel.13787

PMID

36734122

PMCID

PMC10086516

PubMedCentral® Posted Date

2-3-2023

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Animals, Male, Mice, Caloric Restriction, Ghrelin, Longevity, Mice, Inbred C57BL, aging, ghrelin agonist, lifespan, mice

Published Open-Access

yes

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