|Rivas, Donato A. -|
|Morris, Evan P. -|
|Fielding, Roger A. -|
Submitted to: Acta Physiologica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 21, 2011
Publication Date: August 20, 2011
Citation: Rivas, D., Morris, E., Fielding, R. 2011. Lipogenic regulators are elevated with age and chronic overload in rat skeletal muscle. Acta Physiologica. 202(4):691-701. Interpretive Summary: Both the amount of muscle mass and strength decline with age, but the loss of muscle strength far surpasses what is expected based on the decline in muscle mass. Interestingly, an increase in body fat has been shown to be a strong predictor of loss of independence in older adults. Furthermore, with aging there is an inability to increase muscle mass in response to exercise. The purpose of this study was to determine the effect of 28 days of resistance exercise on the storage of fat in muscle and selected proteins that regulate making and burning fat as a fuel. The amount of these fat regulators was determined in the muscle of young (6-month-old) and aged (30-month-old) rats after exercise. We showed that age-induced increases of fat in muscle are associated with more genes that make fat in muscle even after exercise, compared to young animals. These data suggest that making fat is increased and burning fat is decreased in ageing skeletal muscle and is not changed by exercise. By determining the role of increased fat storage on skeletal muscle mass during aging, possible targets for the treatment of age-related muscle loss may be identified.
Technical Abstract: Both muscle mass and strength decline with ageing, but the loss of strength far surpasses what is projected based on the decline in mass. Interestingly, the accumulation of fat mass has been shown to be a strong predictor of functional loss and disability. Furthermore, there is a known attenuated hypertrophic response to skeletal muscle overload with ageing. The purpose of this study was to determine the effect of 28 days of overload on the storage of intramuscular triglycerides (IMTG) and metabolic regulators of lipid synthesis in young and old skeletal muscle. Methods: The phosphorylation and expression of essential lipogenic regulators were determined in the plantaris of young (YNG; 6-month-old) and aged (OLD; 30-month-old) rats subjected to bilateral synergist ablation (SA) of two-thirds of the gastrocnemius muscle or sham surgery. Results: We demonstrate that age-induced increases in IMTG are associated with enhancements in the expression of lipogenic regulators in muscle. We also show that the phosphorylation and concentration of the 5'AMP-activated protein kinase (AMPK) isoforms are altered in OLD. We observed increases in the expression of lipogenic regulators and AMPK signaling after SA in YNG, despite no increase in IMTG. Markers of oxidative capacity were increased in YNG after SA. These overload-induced effects were blunted in OLD. Conclusion: These data suggest that lipid metabolism may be altered in ageing skeletal muscle and is unaffected by mechanical overload via SA. By determining the role of increased lipid storage on skeletal muscle mass during ageing, possible gene targets for the treatment of sarcopenia may be identified.