The impact of biological sex on age-associated alterations to cardiac contractile function

Cardiovascular disease has been the leading cause of death in Canada for the past 25 years. Although cardiovascular disease most commonly occurs in the elderly, the effect of age itself on the heart is still not fully understood. Studies have shown that the ability of the heart to contract forcefully during exercise declines with age. Similar changes have been reported in individual heart cells, indicating that defects in contraction may develop at the cellular level. As the heart needs calcium to contract, one possibility is that the control of calcium levels inside heart cells changes with age. It is also known that men and women are susceptible to different heart diseases. This indicates that age may modify heart function differently in males and females. These sex differences may be caused by differences in individual heart cells. Indeed in our lab we have seen that an age-related decline in heart cell function occurs primarily in cells from male mice, but not in cells from female mice. Although this sex difference is not fully understood, the hormone estrogen may help protect in the female heart from the detrimental effects of age on heart cell function. My proposed research will examine the role of estrogen in heart cell function in young adult and aged female mice. By using mice that have had their ovaries removed at a young age, we will look how removal of estrogen impacts heart cell function later in life. My research will also examine proteins that control calcium within heart cells of male and female mice. As too much calcium in the heart can disrupt heart function, determining differences in the way cells from males and females control calcium may shed light on why men and women are susceptible to different cardiovascular diseases. In the long term, these findings may help identify new drug targets at the cellular level and may optimize the treatment of heart diseases in older men and women.