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Ang-(1-7) protects skeletal muscle function in aged mice
Ying Li1, Jiao Song1, Yangyang Jiang1
1The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Sichuan, China.
BMC Musculoskeletal Disorders
|September 22, 2021
Summary
The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-(1-7)) axis protects against age-related skeletal muscle decline. Exogenous Ang-(1-7) administration can delay this decline, preserving muscle function.
Area of Science:
- Physiology
- Molecular Biology
- Gerontology
Background:
- The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7 (Ang-(1-7)) axis is recognized for its protective role against age-related skeletal muscle dysfunction.
- This study investigates the specific protective effects of ACE2 in mitigating age-associated skeletal muscle decline and elucidates underlying molecular mechanisms.
Purpose of the Study:
- To investigate the protective effects of ACE2 in mitigating age-associated skeletal muscle decline.
- To identify the molecular mechanisms underlying the protective role of the ACE2/Ang-(1-7) axis in skeletal muscle.
- To assess the therapeutic potential of exogenous Ang-(1-7) in counteracting age-related muscle dysfunction.
Main Methods:
- Measured Ang-(1-7) levels and skeletal muscle function in C57BL/6J mice across different age groups.
- Investigated myocyte enhancer factor 2A (MEF2A) expression and its relation to muscle function in ACE2 knockout (ACE2KO) mice.
- Administered Ang-(1-7) to aged ACE2KO mice, assessing MEF2A levels and muscle function pre- and post-treatment.
- Evaluated the in vitro effects of Ang-(1-7) on C2C12 cell growth, differentiation, and glucose transporter type 4 (Glut4) expression.
Main Results:
- Aged mice exhibited reduced skeletal muscle function and lower Ang-(1-7) levels compared to younger mice.
- ACE2KO mice displayed significantly diminished skeletal muscle function and MEF2A protein expression versus wild-type controls.
- Four weeks of Ang-(1-7) treatment in aged ACE2KO mice improved skeletal muscle function, with MEF2A levels remaining unchanged.
- In vitro studies demonstrated that Ang-(1-7) promotes C2C12 cell growth and differentiation, accompanied by upregulated Glut4 expression.
Conclusions:
- The ACE2/Ang-(1-7) axis plays a crucial protective role in maintaining skeletal muscle health.
- Exogenous administration of Ang-(1-7) shows potential in delaying age-related decline in skeletal muscle function.
- The findings suggest Ang-(1-7) may influence glucose metabolism and cellular processes vital for muscle maintenance.
