Increased ceramide content and NFκB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males

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 NFκB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at rest and anabolic and NFκB signaling after an acute bout of high-intensity resistance 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 NFκB 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.

Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans

“…Of note, the exercise-induced increase in muscle C16:0 and C18:0 ceramide was exacerbated in obese and type 2 diabetic individuals compared with athletes, despite lower mRNA expression for ceramide synthesis genes. Recently, C16:0 muscle ceramide accumulation was found to inhibit anabolic signalling after resistance exercise in older humans [44]. Thus, the exaggerated increase in these ceramide species with exercise in obese and type 2 diabetic individuals may attenuate contraction-induced skeletal muscle adaptations and promote sarcopenia in insulin-resistant individuals.…”

Effect of Procysteine on aging-associated changes in hepatic GSH and SMase: evidence for transcriptional regulation of smpd3

“…It seems that ceramides with various chain lengths can be generated in a specifi c manner and have distinct bioactivities ( 50 ). The effects of aging on the FA composition of ceramide have been investigated in several models including mouse CD4+ T-cells ( 51 ), cardiomyocytes ( 52 ), and skeletal muscle ( 53 ). Our mass spectrometry-based analysis of ceramide species in the livers of aged and young mice reveals that aging leads to the accumulation of C16:0 and C24:1 ceramides and has no effect on the less abundant C18:0, C18:1, and C24:0 ceramides, while the level of C20:0 ceramide is modestly suppressed.…”

Ageing, adipose tissue, fatty acids and inflammation

“…In aged males elevated ceramides in skeletal muscles were postulated to contribute to reduction in function in resistance exercise (Rivas et al 2012), with further studies in humans supporting an elevation of ceramides with age (Giusto et al 1992). These findings are reflected in animal studies (Claycombe et al 2002;Lightle et al 2000;Ohanian et al 2014;Perez et al 2005;Rodriguez-Calvo et al 2007;Wu et al 2007;Youm et al 2012), and in vitro cell culture models of senescence (Venable et al 2006) Beyond insulin resistance, accumulation of lipid in skeletal muscle is detrimental to mitochondrial function.…”