Effects of myostatin deletion in aging mice

<jats:title>Summary</jats:title><jats:p>Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging‐related muscle loss. Knock‐out (KO) mouse studies suggest myostatin also affects adiposity, glucose handling and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b31">Morissette <jats:italic>et al.,</jats:italic> 2006)</jats:ext-link>, a concern because of cardiac hypertrophy is associated with adverse clinical outcomes. Therefore, we examined the systemic and cardiac effects of myostatin deletion in aged mice (27–30 months old). Heart mass increased comparably in both wild‐type (WT) and KO mice. Aged KO mice maintained twice as much quadriceps mass as aged WT; however, both groups lost the same percentage (36%) of adult muscle mass. Dual‐energy X‐ray absorptiometry revealed increased bone density, mineral content, and area in aged KO vs. aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1% vs. 49.4%, <jats:italic>P</jats:italic> = 0.002) and smaller left ventricular diastolic diameters (3.41 vs. 2.71, <jats:italic>P</jats:italic> = 0.012) in KO vs. WT mice. Phospholamban phosphorylation was increased 3.3‐fold in KO hearts (<jats:italic>P</jats:italic> < 0.05), without changes in total phospholamban, sarco(endo)plasmic reticulum calcium ATPase 2a or calsequestrin. Aged KO hearts showed less fibrosis by Masson’s Trichrome staining. Thus, myostatin deletion does not affect aging‐related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well.</jats:p>