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.

Vitamin D receptors have been shown to be present in human skeletal muscle using different techniques. We developed a multi-staining immunofluorescent method to detect vitamin D receptor expression and co-localize it with myosin heavy chain isoform expression in skeletal muscle biopsies in older female subjects. Serial sections were cut from frozen samples obtained by needle biopsy of the vastus lateralis. Samples were probed with a primary vitamin D receptor monoclonal antibody and then re-probed with a type IIa myosin heavy chain isoform-specific antibody. IndependentCorrespondence to: Lisa Ceglia, lisa.ceglia@tufts.edu. None of the authors had any conflicts of interest. NIH Public Access

24% higher in Y SA and O SA compared with CON ( p = .009). Eukaryotic initiation factor 2B e phosphorylation was 33% and 9% higher in Y SA and O SA compared with CON ( p = .04). Translational signaling in young adult and aged plantaris muscle is equally responsive to chronic overload.

Aim 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 signalling 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.

Increased intramuscular lipid content has previously been noted in lean and obese elderly persons and is thought to be associated with muscle attenuation, insulin resistance and decreased muscle quality. However, it is still unknown by what exact mechanisms these increases in intramuscular lipids occur and what effect mechanical overload has on lipid metabolic regulators in aged skeletal muscle. The purpose of this study was to determined the effect of 28 days of overload on the storage of intramuscular triglycerides (IMTG) and metabolic regulators (SREBP1, AMPK) of lipid synthesis in the plantaris of young (YNG; 6‐month old) and aged (OLD; 30‐month old) Fischer 344 x Brown Norway rats subjected to bilateral synergist ablation (SA) of two thirds of the gastrocnemius muscle or sham surgery (CON). There was a ~43% increase in IMTG in OLD CON (p<0.05 vs. YNG CON) and SA had no effect on IMTG levels in either group. There was a 41% increase in the expression of the active cleaved form of sterol‐regulatory binding protein 1 (SREBP1) in OLD (p<0.05 vs. YNG CON). SA had no effect on the expression of SREBP1 in OLD SA but was significantly increased in YNG SA (p<0.05 vs. YNG CON). There was no difference in the expression of the full form of SREBP1 between groups. There was a ~20% increase in the expression of the AMP‐activated protein kinase (AMPK) catalytic subunit α1 isoform in the OLD CON (p<0.05 vs. YNG CON). SA had no effect on the expression of AMPK α1 isoform in OLD SA but increased the expression in YNG SA ~20% (p<0.05 vs. YNG CON). There was no change in the expression of the AMPK α2 isoform between groups. These data suggest that the regulation of lipid metabolism is impaired in aging skeletal muscle and does not respond to mechanical overload via SA.