Alterations in Oxygen Consumption, Respiratory Quotient, and Heat Production in Long-Lived GHRKO and Ames Dwarf Mice, and Short-Lived bGH Transgenic Mice
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Growth hormone (GH) signaling influences longevity in mice, with decreased GH signaling associated with longer life span and increased GH signaling with shortened life span. A proposed mechanism through which GH signaling influences life span postulates that decreased GH signaling lowers metabolic rate, thus slowing aging by decreasing production of damaging free radicals. The influence of altered GH signaling on metabolism was tested by monitoring oxygen consumption (VO(2)), respiratory quotient (RQ), and heat production in long-lived GH receptor knockout (GHRKO) and Ames dwarf mice, and short-lived bovine GH-overexpressing transgenic (bGH TG) mice. Intriguingly, both GHRKO and Ames dwarf mice have increased VO(2) and heat per gram body weight, and decreased RQ, whereas bGH TG mice have decreased VO(2) and heat per gram body weight and increased RQ. In conclusion, decreased GH signaling associates with increased metabolism per body weight and may beneficially affect mitochondrial flexibility by increasing the capacity for fat oxidation; generally, GH excess produces opposite metabolic effects.
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In long-lived Ames dwarf and GHR-KO mice with GH-IGF1 signalling defects, mitochondrial bioenergetics is markedly improved, shown by a shift to β-oxidation, increased oxygen consumption rate, and decreased respiratory quotient.
“In the long-lived Ames dwarf mice and growth hormone receptor knockout (GHR-KO) mice, which develop defects in the GH–IGF1 signalling pathway, mitochondrial bioenergetics is markedly improved. This improvement was demonstrated by the metabolic shift to β-oxidation, increased oxygen consumption rate and decreased respiratory quotient25”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [25]
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- Authors
- Westbrook, R., Bonkowski, M. S., Strader, A. D., & Bartke, A.
- Affiliations
- SIU Medicine (US)
- Southern Illinois University Carbondale (US)
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-13
- Volume
- 64A
- Issue
- 4
- Pages
- 443-451
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC2657169
- OpenAlex
- W2105303800
- Cited by
- 143
- References
- 50
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 12 · 2022: 7 · 2021: 9 · 2020: 12 · 2019: 12 · 2018: 9 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 9 · 2012: 9
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Ellison Medical Foundation (AG019899)
- National Institutes of Health
- National Institute on Aging (R01AG019899, AG019899, U19AG023122)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Physical Sciences › Environmental Science › Ecology › Physiological and biochemical adaptations
- Keywords
- growth hormone signaling, longevity, oxygen consumption, respiratory quotient, thermogenesis, metabolic rate, Ames dwarf mice, fat oxidation, aging, free radicals
- MeSH terms
- Aging, Animals, Calorimetry, Indirect, Dwarfism, Longevity, Male, Mice, Mutant Strains, Mice, Transgenic, Oxygen Consumption, Probability, Pulmonary Gas Exchange, Random Allocation, Receptors, Somatotropin, Sensitivity and Specificity, Thyroid Hormones, Signal Transduction, Mice, Knockout, Thermogenesis, Models, Animal, Mice
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