Back to Search
Start Over
Metformin Treatment in Old Rats and Effects on Mitochondrial Integrity
- Source :
- Rejuvenation Res
- Publication Year :
- 2021
- Publisher :
- Mary Ann Liebert Inc, 2021.
-
Abstract
- Metformin, a commonly used, well-tolerated treatment for type 2 diabetes, is being deployed in clinical trials to ameliorate aging in older non-diabetic humans. Concerningly, some experiments in model organisms have suggested that metformin use at old ages shortens lifespan and is toxic to mitochondria. The demonstrated safety of metformin therapy in humans and the conflicting data from model organisms compelled us to test the hypothesis that metformin treatment would be toxic to older rats. To define an effective dose in 30-month-old hybrid rats, we evaluated two doses of metformin (0.1%, 0.75% of the diet) and treated the rats for four months. Body mass decreased at the 0.75% dose. Neither dose affected mortality between 30- and 34-months of age. We assessed mitochondrial integrity by measuring mitochondrial DNA copy number and deletion mutation frequency, and mitochondrial respiration in skeletal muscle and the heart. In skeletal muscle, we observed no effect of metformin on quadriceps mass, mtDNA copy number, or deletion frequency. In the heart, metformin-treated rats had higher mtDNA copy number, lower cardiac mass, with no change in mtDNA deletion frequency. Metformin treatment resulted in lower mitochondrial Complex I-dependent respiration in the heart. We found that, in old rats, metformin did not compromise mitochondrial DNA integrity, did not affect mortality, and may have cardiac benefits. These data provide some reassurance that a metformin intervention in aged mammals is not toxic at appropriate doses.
- Subjects :
- Aging
medicine.medical_specialty
Mitochondrial DNA
endocrine system diseases
ved/biology.organism_classification_rank.species
Type 2 diabetes
Mitochondrion
DNA, Mitochondrial
Internal medicine
Respiration
medicine
Animals
Model organism
ved/biology
business.industry
nutritional and metabolic diseases
Skeletal muscle
Original Articles
medicine.disease
Effective dose (pharmacology)
Metformin
Mitochondria
Rats
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus, Type 2
Geriatrics and Gerontology
business
medicine.drug
Subjects
Details
- ISSN :
- 15578577 and 15491684
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Rejuvenation Research
- Accession number :
- edsair.doi.dedup.....16d34b37f7d4345c672b5d321724e2a4