Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle with age and endurance exercise training

Abstract

Aging is associated with reduced muscle strength and atrophy of type II muscle fibers. Muscle fiber type and contractile function are primarily determined by myosin heavy chain (MHC) isoforms. There are few data available on the effects of aging on MHC isoform expression in humans. In the present study, we tested the hypothesis that MHC isoform protein composition and mRNA abundance would favor a fast-to-slow isoform shift with aging and in response to endurance exercise training. Muscle biopsies were obtained from previously sedentary, healthy men and women, aged 21-87 yr before (n = 77) and after (n = 65) 16 wk of bicycle training (up to 45 min at 80% peak heart rate, 3-4 days/wk). At baseline, MHC I mRNA was unchanged with age, whereas IIa and IIx declined by 14 and 10% per decade, respectively (P < 0.001). MHC IIa and IIx protein declined by 3 and 1% per decade with a reciprocal increase in MHC I (P < 0.05). After training, MHC I and IIa mRNA increased by 61 and 99%, respectively, and IIx decreased by 50% (all P < 0.001). The increase in MHC I mRNA was positively associated with age, whereas the changes in MHC IIa and IIx mRNA were similar across age. MHC I protein increased by 6% and was positively related to age, whereas IIx decreased by 5% and was inversely related to age. These results suggest that the altered expression of MHC isoforms with aging is transcriptionally regulated. In response to endurance exercise, regulation of MHC isoform transcripts remains robust in older muscle, but this did not result in corresponding changes in MHC protein expression.

Myosin and actin expression and oxidation in aging muscle

“…The preferential reduction in myosin content leads to altered stoichiometry of the myofibrillar proteins. This finding is supported by data showing a significant reduction in muscle protein synthesis rates with age (1,34,38,42). The preferential decrease in myosin expression with age compared with actin expression is consistent with previous studies investigating synthesis rates of the different myofibrillar proteins (1, 2).…”

Fiber Types in Mammalian Skeletal Muscles

“…Rat skeletal muscles undergo a type 2B to 2X switching in aging fast muscles and a type 2A to type 1 switching in slow soleus (462)(463)(464). The histochemical fiber type profile does not appear to change with age in human skeletal muscle; however, the relative proportion of fast MyHCs is reduced in elderly subjects (423,733) due to greater atrophy of type 2 fibers (478). The greater susceptibility of type 2B fibers (2X fibers in human muscle) to aging may be due to neurogenic changes leading to selective denervation of these fibers, reflected by fiber type-specific endplate fragmentation (773).…”

Skeletal muscle energetics with PNMR: personal views and historic perspectives

“…With aging, the loss of type II muscle fibers (fast twitch) is greater than type I muscle fibers (slow twitch). Moreover, aging-associated adaptation of muscle fibers to more efficient type I muscle fiber has been shown (124). The findings of 31 P MRS studies on aging are still a matter of debate, and the topic of metabolic capacity associated with aging and fiber type has yet to be resolved.…”