The effect of a pharmaceutical ghrelin agonist on lifespan in C57BL/6J male mice: A controlled experiment
Open accessAbstract
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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The neuroprotective effects of ghrelin might be attributed to its ability to impact age-related pathways, including sirtuin-1 activation, and to prolong lifespan in different mouse models of aging.
“The neuroprotective effects of ghrelin might be attributed to its ability to impact age-related pathways, including sirtuin-1 activation, with studies demonstrating its ability to prolong lifespan in different mouse models of aging.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [558]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Kaiser, K. A., Kadish, I., van Groen, T., Smith, D. L., Dickinson, S., Henschel, B., Parker, E. S., Brown, A. W., & Allison, D. B.
- Affiliations
- University of Alabama at Birmingham (US)
- Department of Cell, Developmental and Integrative Biology, School of Medicine University of Alabama at Birmingham Birmingham Alabama USA
- Indiana University Bloomington (US)
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Kaiser, Kathryn A.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2023-02-03
- Volume
- 22
- Issue
- 4
- Pages
- e13787-e13787
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC10086516
- OpenAlex
- W4319063365
- Cited by
- 5
- References
- 23
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056336)
- National Institute on Aging (P30 AG050886, P30NS47466, R01AG043972)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- ghrelin agonists, lifespan extension, longevity, hunger, dietary intake, pair feeding, caloric restriction, energy sensing, C57BL/6J mice, hypothalamic signaling
- MeSH terms
- Animals, Longevity, Male, Mice, Inbred C57BL, Caloric Restriction, Mice, Ghrelin
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