Grant: Fellowship - Priority Announcement: Aging

Menopause occurs when the ovaries no longer contain eggs that produce estrogen. This leads to many physical changes and 75% of women report that these changes have negatively impacted their quality of life. Many years after this menopausal transition, studies have shown that postmenopausal women are frailer and more prone to chronic illness than men. Although estrogen therapy can be used to manage the symptoms of menopause, it cannot be used indefinitely as prolonged estrogen use comes with its own health risks. Up till now, there has been little consideration for the biology of menopause but without knowing more, we cannot suggest better treatment options. For this reason, our laboratory has launched a research program to further investigate this topic and our initial findings are promising. Using a mouse model of menopause, we have confirmed that estrogen loss can accelerate cellular aging across many organ systems and that these mice show early signs of disease. This rapid build-up of aged cells makes it difficult for tissues to regenerate, leading to their diminished function. At the molecular level, aged cells are recognizable from young, healthy cells so we have capitalized on this difference to develop drugs that can selectively remove those aged cells. Remarkably, cells and tissue from postmenopausal mice treated with these drugs did not show signs of aging nor health decline. We are now aiming to understand the complex mechanisms governing this process using cutting edge technology that can track the molecular changes of individual cells in mice as they undergo menopause, and are taking the first steps to translate our findings in women. We hope that our work will eventually give rise to future projects aimed at developing treatments and screening tools. With 40% of women currently over 50, this highlights the high social and economic potential of this work.