Keck School of Medicine Events

Keck School of Medicine of USC Research Seminar Series

"Mitochondrial-Derived Peptides and their Role in Health and Disease"
February 2013
Monday, February 4, 2013
11:30 AM - 1:00 PM
Aresty Auditorium, Harlyne J. Norris Research Tower (NRT)
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Dean Pinchas Cohen, MD, Dean of the USC Davis School of Gerontology; Professor of Gerontology and Medicine; Executive Director, Ethel Percy Andrus Gerontology Center, University of Southern California, will be presenting. Dr. Thomas Buchanan will be presenting the introduction. A light lunch will be served before the Seminar at 11:30 am.
Abstract: Mitochondria contain >1000 nuclear proteins, but the mitochondrial-chromosome only encodes 13 proteins. Humanin; a novel 24AA peptide encoded from the 16S rRNA region of the mtDNA is a potent neurosurvival factor shown to be cytoprotective and metaboloprotective in vitro and in vivo, in models of aging-related diseases. We developed a humanin ELISA assay and demonstrated that humanin declines with aging and its levels are altered in states of insulin resistance, endothelial-dysfunction and neurodegeneration. In vivo administration of humanin reverses pathological processes involved with diabetes, atherosclerosis and Alzheimer's disease. We recently identified an additional six peptides encoded from ORFs within the 16S rRNA, which we named SHLPs (small humanin-like peptides). Analysis of their expression reveals that they are transcribed in the mitochondria from mtDNA, are detectable in plasma, and exhibit tissue-specific distribution and age dependency. SHLPs 1-5 act as potent bioactive molecules acting to induce cell protection and ROS inhibition (like humanin, via activation of Erk and Stat3 phosphorylation) but with different temporal profiles, suggesting that these peptides may act in concert. SHLP6 has opposing actions, potently inducing apoptosis. These observations reveal that the mitochondria possess previously unappreciated roles in the regulation of metabolism and apoptosis that occur via the synthesis of mitochondrial-derived peptides (MDPs). We propose that the mitochondrial peptidome could explain important new aspects of mitochondrial biology and dysfunction with relevance to human biology and disease and that the novel MDPs we describe here may represent retrograde communication signals from the mitochondria that are critical to the aging process and aging related diseases. Biography: Dr. Cohen is the Dean of the USC Davis School of Gerontology and serves as the Executive Director of the Ethel Percy Andrus Gerontology Center. He graduated in 1986 with highest honors from the Technion Medical School in Israel and trained at Stanford University. He held faculty positions at the University of Pennsylvania and UCLA. He received numerous awards for his research, including an NIA "EUREKA" Award and the Transformative RO1-Grant from the Director of National Institutes of Health. He also received the Glenn Award for Research in Aging. Dr. Cohen published over 250 papers in top scientific journals focusing on aging, cancer, and diabetes; with an emphasis on the emerging science of mitochondrial-derived peptides, which he discovered. He holds several patents for novel peptides and is the Co-founder of CohBar, a biotechnology company developing mitochondrial peptides for diseases of aging. His work has been cited in the Los Angeles Times and the New York Times. He serves on the boards of several professional journals and societies, including the American Federation for Aging Research. Dr. Cohen is president-elect of the Growth Hormone Society and served on the Endocrine Society Steering Committee.

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