Effect of age on basal muscle protein synthesis and mTORC1 signaling in a large cohort of young and older men and women

Abstract

The rate of muscle loss with aging is higher in men than women. However, women have smaller muscles throughout the adult life. Protein content is a major determinant of skeletal muscle size. This study was designed to determine if age and sex differentially impact basal muscle protein synthesis and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling. We performed a secondary data analysis on a cohort of 215 healthy, non-obese (BMI<30kg·m(-2)) young (18-40y; 74 men, 52 women) and older (60-87y; 57 men, 32 women) adults. The database contained information on physical characteristics, basal muscle protein fractional synthetic rate (FSR; n=215; stable isotope methodology) and mTORC1 signaling (n=125, Western blotting). FSR and mTORC1 signaling were measured at rest and after an overnight fast. mTORC1 and S6K1 phosphorylation were higher (p<0.05) in older subjects with no sex differences. However, there were no age or sex differences or interaction for muscle FSR (p>0.05). Body mass index, fat free mass, or body fat was not a significant covariate and did not influence the results. We conclude that age and sex do not influence basal muscle protein synthesis. However, basal mTORC1 hyperphosphorylation in the elderly may contribute to insulin resistance and the age-related anabolic resistance of skeletal muscle protein metabolism to nutrition and exercise.

Keywords: Aging; Gender; Protein metabolism; Sarcopenia; Stable isotopes; mTOR.

Figure 1

Average yearly mixed muscle protein synthesis rates (FSR) over time. The FSR from our laboratory was stable (intraclass correlation coefficient = 0.10) over the 10-year period in which the data from our cohort of 215 subjects was collected.

Figure 2

Basal, post-absorptive mixed muscle protein synthesis rates (FSR) in young men (n=74), and women (n=52), and older men (n=57) and women (n=32). There were no significant differences between groups or sex-age interaction.

Figure 3

Representative immunoblot blots of phosphylated mammalian target of rapamycin (mTOR), S6 kinase (S6K)1, eukaryotic initiation factor 4E-binding protein (4E-BP)1 for each group.