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Sustained overexpression of IGF-1 prevents age-dependent decrease in charge movement and intracellular Ca(2+) in
Zhong-Min Wang1, María Laura Messi, Osvaldo Delbono
1Department of Physiology and Pharmacology, Gerontology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Biophysical Journal
|February 28, 2002
Summary
Overexpression of insulin-like growth factor 1 (IGF-1) in skeletal muscle prevents age-related decline in muscle fiber charge movement and intracellular calcium levels. This finding suggests IGF-1 as a potential therapeutic target for age-related muscle dysfunction.
Area of Science:
- Skeletal Muscle Physiology
- Aging Research
- Molecular Biology
Background:
- Age-dependent decline in skeletal muscle function is a significant health concern.
- Reduced charge movement and intracellular calcium handling are implicated in age-related muscle weakness.
- Insulin-like growth factor 1 (IGF-1) plays a crucial role in muscle development and maintenance.
Purpose of the Study:
- To test the hypothesis that sustained transgenic overexpression of IGF-1 prevents age-dependent decreases in skeletal muscle fiber charge movement and intracellular calcium.
- To investigate the effects of IGF-1 on age-related changes in muscle electrophysiology and calcium dynamics.
Main Methods:
- Studied short flexor digitorum brevis (FDB) muscle fibers from young (5-7 months) and old (21-24 months) wild-type and IGF-1 transgenic mice.
- Utilized the patch-clamp technique in the whole-cell configuration to measure charge movement (Qmax) and intracellular calcium concentration ([Ca2+]i).
- Simultaneously recorded charge movement and intracellular calcium concentration in voltage-clamped muscle fibers.
Main Results:
- Old wild-type mice showed a significant age-dependent reduction in charge movement (36 +/- 2.1 nC microF(-1)) compared to young wild-type mice (52 +/- 2.1 nC microF(-1)).
- Old IGF-1 transgenic mice maintained significantly higher charge movement (49 +/- 2.3 nC microF(-1)) compared to old wild-type mice, similar to young mice.
- Peak intracellular calcium ([Ca2+]i) significantly decreased with age in wild-type mice (9.9 +/- 0.1 muM) but was preserved in IGF-1 transgenic mice (14 +/- 1.1 muM).
Conclusions:
- Sustained overexpression of IGF-1 in skeletal muscle effectively prevents age-dependent reductions in charge movement.
- IGF-1 overexpression also preserves age-related declines in peak intracellular calcium concentration in skeletal muscle fibers.
- These findings highlight the potential of IGF-1 to counteract age-related skeletal muscle dysfunction.