Expression of Contractile Proteins in the Heart Changes with Age
Contractile proteins embedded into the cell cytoskeleton enable muscle cells to change shape in response to stimulus from the nervous system. Here researchers explore age-related changes in these proteins in the heart, finding that the balance of what are thought to be the most important contractile proteins shifts to favor a less effective variant. This may be a maladaptive side-effect, however, and not necessarily the important driver of age-related declines in the ability of heart muscle to contract. Testing that proposition in mice would be fairly straightforward; one could use gene therapies or genetic engineering to rebalance contractile protein expression in favor of the more effective variant and see what happens.
The present study demonstrates that the expression of both cardiac contractile and regulatory proteins is altered during aging, and these changes contribute to the contractile deficits that are associated with aging. Our data show that during aging there is a significant increase in the expression of cardiac myosin heavy chain β (β-MyHC) and phosphorylation of both troponin I (TnI) and myosin-binding protein C (MyBP-C). Similar to our results, others have demonstrated an increase in cardiac β-MyHC during aging.
Cardiac myosin heavy chain α (α-MyHC) has been demonstrated to have a ~2-3 fold higher actin-activated ATPase and velocity of actin movement in the motility assay than cardiac β-MyHC. Additionally, in large mammals, cardiac α-MyHC produces an ~2x higher force compared to cardiac β-MyHC, while there is no difference in force for α-MyHC and β-MyHC in smaller mammals including the mouse and rat. Thus, the increase in the expression of β-MyHC in cardiac muscle during aging documented in the present study would be expected to result in a reduction in rate constant of force redevelopment after quick release and restretch (Ktr) and a decrease the rates of sarcomere length (SL) shortening and relaxation of single cardiomyocytes.
Aging is also well known to be associated with an increase in myocyte size and cardiac fibrosis, which is consistent with our results. Further, despite the increase in myocyte size, total MyHC expression did not change, and thus, the number of myosin filaments per myocyte cross-section would decrease and coupled with the increase in cardiac fibrosis would be expected to contribute to the decrease in the maximally Ca2+ activated force/cross-section in 24 months old rats.
Seems to me this an adaptive response to stiffing of the vascular system.