Insulin-like growth factor-1 prevents age-related decrease in specific force and intracellular Ca2+ in single intact muscle fibres from transgenic mice.

Abstract

In the present work we test the hypothesis that sustained transgenic overexpression of insulin-like growth factor-1 (IGF-1) in skeletal muscle prevents age-related decreases in myoplasmic Ca2+ concentration and consequently in specific force in single intact fibres from the flexor digitorum brevis (FDB) muscle from the mouse. Measurements of IGF-1 concentration in FDB muscle showed higher levels in transgenic than in wild-type mice at all ages. The specific tetanic force decreased significantly in single muscle fibres from old (286 +/- 22 kPa) compared to young wild-type (455 +/- 28 kPa), young transgenic (423 +/- 43 kPa), and old transgenic mice (386 +/- 15 kPa) (P < 0.05). These results are consistent with measurements in whole FDB muscles. The peak Ca2+ concentration values in response to prolonged stimulation were: 1.47 +/- 0.15, 1.70 +/- 0.29, 0.97 +/- 0.13 and 1.7 +/- 0.22 microM, in fibres from young wild-type, young transgenic, old wild-type and old transgenic mice, respectively. The effects of caffeine on FDB fibres support the conclusion that the age-related decline in peak myoplasmic Ca2+ and specific force is not explained by sarcoplasmic reticulum Ca2+ depletion. Immunohistochemistry in muscle cross-sections was performed to determine whether age and/or IGF-1 overexpression induce changes in fibre type composition. The relative percentages of type IIa, IIx and I myosin heavy chain (MHC) isoforms did not change significantly with age or genotype. Therefore, IGF-1 prevents age-related decline in peak intracellular Ca2+ and specific force in a muscle that does not exhibit changes in fibre type composition with senescence.