|Rivas, Donato -|
|Morris, Evan -|
|Haran, Prashanth -|
|Pasha, Evan -|
|Morais, Mauricio Da Sil -|
|Dolnikowski, Gregory -|
|Phillips, Edward -|
|Fielding, Roger -|
Submitted to: Journal of Applied Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 2, 2012
Publication Date: December 1, 2012
Citation: Rivas, D.A., Morris, E.P., Haran, P.H., Pasha, E.P., Morais, M.V., Dolnikowski, G., Phillips, E.M., Fielding, R.A. 2012. Increased ceramide content and NFkB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males. Journal of Applied Physiology. 113(11):1726-1736. Interpretive Summary: The ability of older individuals to respond to a single bout of strength exercise declines with age. This decline has been found to be linked to the loss of skeletal muscle and functional ability (Sarcopenia). In addition to the known loss of skeletal muscle with aging there is also an increase in fat stored within skeletal muscle. We believe certain types of these fats (ceramides) have a role in the inability of aged muscle to respond to strength exercise. Therefore, we compared the amount of stored ceramide content and both the negative and positive regulators muscle growth in the skeletal muscle of healthy, young (9) and older (10) males before and after a single bout of high-intensity strength exercise. We observed that specific types of ceramides (C16:0) are associated with lower leg lean mass in males. This may be associated with increases in the pro-inflammatory molecule NFkB (Nuclear Factor Kappa Beta) which mediates the production of proteins with the ability to inhibit pathways that control muscle growth. We conclude that ceramides may have a significant role in the inability of skeletal muscle to respond to strength exercise and maintaining lean mass that is observed with aging.
Technical Abstract: One of the most fundamental adaptive physiological events is the response of skeletal muscle to high-intensity resistance exercise, resulting in increased protein synthesis and ultimately larger muscle mass. However, muscle growth in response to contraction is attenuated in older humans. Impaired contractile-induced muscle growth may contribute to sarcopenia: the age-associated loss of muscle mass and function that is manifested by loss of strength, contractile capacity and endurance. We hypothesized that the storage of ceramide would be increased in older individuals and this would be associated with increases in NFkB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at baseline and anabolic and NFkB signaling after and acute bout of high-intensity exercise in young and older males. Using lipidomics analysis we show there was a 156% increase in the accumulation of C16:0-ceramide (P<0.05) and a 30% increase in C20:0-ceramide (P<0.05) in skeletal muscle with aging, although there was no observable difference in total ceramide. C16:0-ceramide content was negatively correlated (P=0.008) with lower leg lean mass. Aging was associated with a ~60% increase in the phosphorylation of the proinflammatory transcription factor NFkB in the total and nuclear cell fractions (P<0.05). Furthermore, there was an attenuated activation of anabolic signaling molecules such as, Akt (P<0.05), FOXO1 (P<0.05) and S6K1 (P<0.05) after an acute bout of high-intensity resistance exercise in older males. We conclude that ceramide may have a significant role in the attenuation of contractile-induced skeletal muscle adaptations and atrophy that is observed with aging.