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A Novel GH Deficient Rat Model Reveals Cross-Species Insights Into Aging
Soe Maung Maung Phone Myint1, Alexander Tate Lasher1, Kaimao Liu1
1Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Aging Cell
|June 6, 2025
Summary
Growth hormone (GH) deficiency in rats significantly reduces body size and increases longevity, mirroring mouse studies. This new rat model offers insights into GH signaling and aging across mammals.
Area of Science:
- Endocrinology
- Aging Research
- Genetics
Background:
- Studies in mice show disrupted growth hormone (GH) signaling increases longevity and improves health.
- Generalizability of these findings to other mammals, particularly rats, is unclear due to limited and inconsistent evidence.
Purpose of the Study:
- To investigate the role of GH signaling in longevity and aging processes across mammalian species.
- To develop and characterize a novel GH-deficient rat model to study aging.
Main Methods:
- Created a GH-deficient rat model using CRISPR/Cas9 technology targeting the GH-releasing hormone (GHRH) gene.
- Physiologically characterized GHRH knockout (KO) rats, including body weight, body fat, insulin sensitivity, IGF-I levels, and energy metabolism via indirect calorimetry.
- Analyzed gut microbial community diversity in adult GHRH-KO rats.
Main Results:
- GHRH-KO rats exhibited half the body weight of wild-type controls.
- KO rats showed increased body fat percentage, enhanced insulin sensitivity, and reduced circulating IGF-I.
- Metabolic analysis revealed decreased reliance on glucose oxidation, and gut microbiome diversity differed between sexes in KO rats compared to controls.
Conclusions:
- The novel GHRH-deficient rat model accurately recapitulates key aspects of the GH activity-deficient phenotype observed in mice.
- This rat model serves as a valuable tool for future research into the mechanisms linking GH signaling to aging and longevity.

