Myosin light chain 3f attenuates age‐induced decline in contractile velocity in MHC type II single muscle fibers

Abstract

Summary Aging is characterized by a progressive loss of muscle mass and impaired contractility (e.g., decline in force, velocity, and power). Although the slowing of contraction speed in aging muscle is well described, the underlying molecular mechanisms responsible for the decrement in speed are unknown. Myosin heavy chain (MHC) isoforms are the primary molecules determining contractile velocity; however, the contraction speed of single fibers within a given MHC isoform type is variable. Recent evidence proposes that the decline in shortening velocity (Vo) with aging is associated with a decrease in the relative content of essential myosin light chain 3f (MLC3f) isoform. In the current study, we first evaluated the relative content of MLC3f isoform and Vo in adult and old rats. We then used recombinant adenovirus (rAd) gene transfer technology to increase MLC3f protein content in the MHC type II semimembranosus muscle (SM). We hypothesized that (i) aging would decrease the relative MLC3f content and Vo in type II fibers, and (ii) increasing the MLC3f content would restore the age-induced decline in Vo. We found that there was an age-related decrement in relative MLC3f content and Vo in MHC type II fibers. Increasing MLC3f content, as indicated by greater % MLC3f and MLC3f/MLC2f ratio, provided significant protection against age-induced decline in Vo without influencing fiber diameter, force generation, MHC isoform distribution, or causing cellular damage. To the best of our knowledge, these are the first data to demonstrate positive effects of MLC3f against slowing of contractile function in aged skeletal muscle.

Amplitude of the actomyosin power stroke depends strongly on the isoform of the myosin essential light chain

“…Absence of the N-terminal extension generates lower force (41), probably causing a less prominent power stroke in S1A2, and is not related to abnormal cardiac function. On the other hand, in the skeletal muscle of aged rats, replacement of A1 in a fraction of heads by A2 improved contractility by increasing the rate of shortening (43). This is consistent with the hypothesis that the N-terminal extension enhances isometric force while slowing the speed of unloaded shortening.…”

Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology

“…Tikunov et al have also found a shift from fast to slow myosin light chain, tropomyosin, and troponin (C, I, and T) isoforms in CHF. Aging causes a decrease in the fast myosin light chain 3 isoform in limb muscle that contributes to slow shortening velocity [115], and this may also occur in the diaphragm. Overall, MHC and thin-filament protein adaptations will compromise diaphragm function during expulsive behaviors as fibers with slow myofibrillar protein isoforms have slower shortening velocity and lower peak power than fibers rich in fast isoforms.…”

Myofilament Protein Alterations Promote Physical Disability in Aging and Disease

“…There are two regulatory (MLC2s, MLC2f) and three essential (MLC1s, MLC1f, MLC3f) isoforms that typically are found in slow-twitch (s or MHC I) and fast-twitch (f or MHC II) fibers, although various combinations of these isoforms are found. The relative proportion of MLCs expressed in individual human fibers does not seem to affect cross-bridge kinetics (17), although it may regulate function in the fastest fibers in lower order mammals (12). On this background, we will now discuss how aging and disease might alter skeletal muscle performance by modulating these molecular functional properties.…”