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As we age, our bodies accumulate sick, senescent cells. These cells, often called zombie cells, promote inflammation, damage neighboring cells, and cannot divide, thus driving disease and aging. While the immune system typically helps the body rid itself of these senescent cells, this process slows down with age and leads to an accumulation of senescent cells. This accumulation of senescent cells is associated with age-related diseases.
Aditi Gurkar, PhD, assistant professor of Medicine at the Aging Institute and Division of Geriatric Medicine, along with her lab and others in the aging research field have previously shown that elimination of such zombie cells using senotherapeutics — drugs which can help the body eliminate these senescent cells — improves health and delays the onset of chronic conditions associated with aging in animal models. Research is now underway to identify and develop senotherapeutics, however some significant challenges still exist. Currently, there is no satisfactory tool to measure senescence load in humans. Without understanding senescent cell load and accumulation in tissues, it will be challenging to translate senotherapeutics into the clinic.
Two recent grants awarded to Dr. Gurkar from the Richard King Mellon Foundation aim to address this fundamental shortcoming. With one of these grants, Dr. Gurkar is working in collaboration with physicist and expert in nanomagnetic materials, Rama Bala, PhD. This project will explore nanomedicine and magnetic force microscopy to quantify changes in senescent cells.
This award not only provides funding for exciting science across disciplines, but also provides unique experiential training opportunities for the next generation of scientists to drive bold research in new directions. Through dedicated mentorship and partnership with STEMnetX — a non-profit STEM empowerment program implemented by the Chance to Change Lives Foundation — this project will allow recruitment of a diverse group of trainees to further scientific discovery in aging research.
The second Richard King Mellon Foundation grant is in partnership with Patricia Opresko, PhD, the Dr. Bernard F. Fisher, Chair for Breast Cancer Discovery Science, co-leader of UPMC Hillman Cancer Center’s Genome Stability Program, and professor of Environmental and Occupational Health in the School of Public Health and in the Department of Pharmacology and Chemical Biology in the School of Medicine at the University of Pittsburgh. This project will explore telomeres — protein-DNA structures that cap chromosome ends and shorten with every cell division — as markers of senescence and aging.
Shortened telomeres are known to trigger replicative senescence, or senescence that is associated with cells that frequently divide. However, most cells in the human body rarely divide. It is now known that cells that do not actively divide — like neurons and cardiomyocytes — also exhibit features of senescence, and that oxidative damage — caused by reactive oxygen species — to telomeres can trigger senescence without shortening. This project will examine whether telomere damage independent of shortening can be used as a detector of senescence in non-dividing cells.
Detection of biological age is a formidable challenge and requires a cross-disciplinary approach. Dr. Gurkar says she is truly honored and excited for this support from the Richard King Mellon Foundation (RKMF), which will allow her to explore novel and innovative ideas in the field of aging research. She envisions that the RKMF grants will support the development of innovative tools to advance aging research and make these discoveries accessible.