Does long time aerobic exercise mitigate age related heart stiffness by altering titin isoforms?

Well, with a topic title like that, I expect an overload of hits.

In 1977 Maruyama described a muscle protein that he named connectin, now more commonly referred to as titin.

Titin is responsible for the passive elasticity of muscles and to prevent muscle over stretching. It is the largest protein in nature and is appropriately  encoded by the largest human gene,  the TTN gene. The titin molecule is the length of the sarcomere stretching from the Z line to the M band in the sarcomere.

Lalande et al (1) describe the link between exercise and titin's properties, specifically passive stiffness.The are a number of titin isoforms, some are long and thin associated with less stiff muscles , while others seem more likely to be related to stiffer muscles.. The authors present animal experiment data  that suggest titin stiffness  can by modified by such post translational mechanisms such as  phosphorylation.

They suggest that "cardiac passive stiffness (k )may be a unifying mechanism "that links the benefits of long time aerobic exercise and the negative cardiovascular effect of sedentary lifestyles.

They review the work of the Dallas group (2) that demonstrated long time endurance athletes have ventricular stiffness similar to that of young sedentary subjects and their meta-analysis (3) that suggested that exercise levels above the US guidelines ( which is 150 minutes of moderate level exercise per week, or 500 Met minutes per week) significantly reduced the risk of diastolic heart failure presumably by mitigating the age and inactivity related increase in cardiac stiffness,

They review animal models that demonstrated exercise induced changes in cardiac passive stiffness that may be related to alterations in titin. To date there are no human data demonstrating that relationship but perhaps post translational alterations in titin offers a mechanism by which endurance exercise maintains cardiac compliance.Anyway it is nice to think so.


1) Lalande, S et al  The link between exercise and titin passive stiffness.Exp Physiology 2017 p 1-12

2)Arbab-Zadeh, A Effect of aging and physical activity of left ventricular compliance. Circulation 110,1799

3)Pandey,A Dose-response relationship between physical activity and risk of heart failure: a meta-analysis. Circulation 132 ,1786