Age-dependent Changes in a Chaperone Complex in the Mouse Heart

The exquisitely organized sarcomere, the unit of contraction of striated muscle, is a very stable structure with a slow turnover rate of its components. The myosin chaperone UNC-45 and its co-chaperones, Hsp90 and Hsp70, are required for the initial folding of the myosin head domain and the assembly of myosin into thick filaments. There is increasing evidence that the UNC-45 chaperone system has an important role during aging to preserve sarcomere organization and myosin levels, and its decline may be a key factor in sarcopenia, the reduced skeletal muscle mass and function found in the elderly without an underlying condition. Cardiac muscle is another type of striated muscle but the role of the UNC-45 system has not yet been examined in the aging heart. Here we show that in the mouse heart, during aging, there is a decline in the levels of myosin, Unc-45b and Hsp70, but not Hsp90, and no obvious changes in sarcomere organization. In contrast, it is known that in skeletal muscle, there is a decline in both Unc-45b and Hsp90, and we show here that there is no decline in Hsp70. The decreased level of Hsp70 specifically in the heart could have broader implications than seem apparent as it could affect the folding and assembly of many other proteins in the aging heart and contribute to cardiomyopathies. Since Hsp70 mediates protein stabilization and prevents protein aggregation, its age-dependent reduction could potentially affect diseases such as amyloidosis.