Mayo Clinic Team Bridging Basic and Clinical Research to Improve Women’s Health Awarded $6.1 Million

The Office of Research on Women’s Health (ORWH) and the National Institute on Aging (NIA) have awarded Mayo Clinic a $6.2 million grant to fund a Specialized Center of Research Excellence (SCORE) on sex differences. The overarching theme of the project, entitled Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer’s Disease, will be to investigate how abrupt loss of ovarian hormones, caused by bilateral salpingo-oophorectomy (BSO) prior to natural menopause, affects overall aging, physical and cognitive function, and risk for AD pathophysiology. Approximately one-in-eight women have their ovaries removed before reaching natural menopause.  Given the large number of aging women with a history of premenopausal BSO, there is an urgent need to understand the long-term physical and cognitive outcomes of the procedure in order to empower women considering prophylactic bilateral oophorectomy in the future to make more informed decisions. Additionally, a more complete understanding of the biological mechanisms that contribute to the harmful outcomes is essential for finding ways to mitigate or prevent them.  The SCORE will be led by PI’s Michelle M. Mielke, PhD, and Virginia M. Miller, PhD.

SCORE grants are designed to promote interdisciplinary approaches to advance translational research on sex differences; to earn these competitive awards, institutions must develop a research agenda bridging basic and clinical research underlying a health issue pertinent to improving the health of women. Centers of Excellence also serve as vital hubs for education and dissemination of innovative sex-based and informed translational research methods and best practices.  They also provide leadership in the development and promotion of standards and policies for the consideration of sex differences in biomedical research.  The Office of Health Disparities Research’s collaboration with the Office of Women’s Health was received positively by the grant reviewers, and assisted in funding of the grant.  The Mayo Clinic SCORE will be comprised of three cores that will support the SCORE research projects and a career development program, and include an Administrative Core (led by Drs. Mielke and Miller), a Career Enhancement Core, (led by Dr. Miller), and a Research Support Core-Clinical Core (led by Ekta Kapoor, MBBS), as well as three research projects:

Project 1:  Effects of Bilateral Oophorectomy on Physical and Cognitive Aging.  This project will assess the effects of premenopausal BSO on accelerated aging, as measured by declines in physical and cognitive function and plasma levels of senescence and other biomarkers of accelerated aging. Leaders: Michelle M. Mielke, PhD and Walter A. Rocca, MD.

Project 2: Bilateral Oophorectomy on Imaging Biomarkers of Alzheimer’s and Cerebrovascular Diseases. This project will assess the effects of premenopausal BSO on neuroimaging measures of Alzheimer’s disease and cerebrovascular pathology, and determine whether APOE ε4 modifies these effects.  Leader: Kejal Kantarci, M.D.

Effects of Ovariectomy on the Biology of Physical and Cognitive Aging in Mice. A mechanistic complement to the human projects, this project will determine the effects of ovariectomy (OVX) in Project 3: mice on cellular senescence and will measure physical and cognitive function. The project will also determine the temporal sequence and tissue-specific effects of estrogen replacement therapy on cellular senescence. Leader: Nathan LeBrasseur, Ph.D. 

OHDR congratulates Drs. Mielke, Miller, and all the SCORE researchers on this exciting sex differences research opportunity!