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Age-Dependent Effects of Adrenomedullin on Muscle Fiber Composition, Angiogenesis, and Muscle Satellite Cells
Ryota Iyama1, Eriko Kurogi2, Takumi Yokokawa3
1Laboratory of Molecular Adaptations to Exercise, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Introduction:
Sarcopenia has recently become a major public health issue. Adrenomedullin (AM) exerts diverse physiological effects, including angiogenesis, but its role in skeletal muscle is unclear. This study investigates whether AM can attenuate sarcopenic changes in aged mice compared to young adults.
Methods:
Young and old male C57BL/6J mice were randomly divided into two groups: the AM-treated group, which received subcutaneous administration of AM (50 nmol/kg body weight) 6 days a week, and the sham-treated group, which was injected with vehicle. After 3 months of treatment, we performed multi-muscle analyses (EDL, SOL, and PLA) using western blotting and immunohistochemistry.
Results:
AM treatment significantly increased AM levels in plasma and muscle tissue. In young mice, AM was associated with changes in muscle fiber-type composition, including a reduction in Type IIx fibers, suggesting muscle-specific functional adaptation. In aged mice, AM increased CD31-positive capillary density and Pax7-positive muscle satellite cells (MuSCs), indicating improved vascular and stem cell niches. These changes occurred without alterations in muscle mass but were accompanied by improved motor function in aged mice.
Conclusions:
AM exerts age-dependent effects on skeletal muscle, with distinct responses observed in young and aged mice. These findings suggest that AM may contribute to muscle adaptation through context-dependent mechanisms involving vascular remodeling and fiber-type modulation.
Insights
Adrenomedullin (AM) shows age-dependent effects on skeletal muscle. In aged mice, AM improved vascularization and muscle stem cells, enhancing motor function without changing muscle mass.
Area of Science:
- Muscle physiology
- Aging research
- Endocrinology
Background:
- Sarcopenia is a growing public health concern.
- Adrenomedullin (AM) has known physiological effects, but its role in skeletal muscle aging is not well understood.
- This study explores AM's potential to counteract age-related muscle decline.
Purpose of the Study:
- To investigate the effects of Adrenomedullin (AM) on sarcopenic changes in aged mice.
- To compare AM's impact on skeletal muscle in young versus aged mice.
Main Methods:
- Young and aged male mice received subcutaneous Adrenomedullin (AM) or vehicle for 3 months.
- Multi-muscle analyses included western blotting and immunohistochemistry.
- Evaluated muscle mass, fiber-type composition, vascularization, and satellite cell populations.
Main Results:
- AM treatment increased AM levels in plasma and muscle.
- In aged mice, AM enhanced capillary density and muscle satellite cells (MuSCs), improving vascular and stem cell niches.
- Aged mice showed improved motor function with AM treatment, despite no change in muscle mass.
Conclusions:
- Adrenomedullin (AM) exhibits age-dependent effects on skeletal muscle.
- AM may promote muscle adaptation via vascular remodeling and fiber-type modulation in an age-specific manner.
- AM presents a potential therapeutic avenue for age-related muscle dysfunction.
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