Grant: Project Grant

As we age, our heart function gradually declines. Older adults often experience changes such as weaker heart pumping, stiffening of blood vessels, irregular heart rhythms, and a higher risk of heart disease. One reason for this decline is that the mitochondria in our heart cells become less efficient as we age. When mitochondria decline in function, they put stress on the cell and may set off harmful reactions that can further damage the heart. This harmful response can make the heart more vulnerable to events like a heart attack. Although heart cells, known as cardiomyocytes, do not normally divide, they can still enter a state called "senescence" where they stop functioning properly and release harmful substances. This damaging process is partly controlled by a cellular alarm system known as the cGAS-STING pathway. Aging makes this worse by further damaging mitochondria, making the heart even more vulnerable to injury. Our previous research found that certain natural fat-based molecules, made by enzymes in the body, help protect mitochondria and reduce heart damage. But another enzyme, called soluble epoxide hydrolase (sEH), quickly breaks down these protective molecules. We discovered that blocking or removing sEH in older animals helped protect the heart by keeping mitochondria healthier. In this project, we aim to explore how turning off sEH specifically in cardiomyocytes might prevent mitochondrial damage, slow down aging processes in the heart, and improve recovery after a heart attack in older individuals.