The focus of Dr. Rabinovitch’s laboratory research is on the use of transgenic mouse models and pharmacological treatments to examine the effects of cell signaling, protein homeostasis and reactive oxygen species (ROS) on lifespan and healthspan. Transgenic mice that overexpress catalase have been found to be protected against multiple health challenges, including cardiac aging, sarcopenia and some cancers. Similar benefits are conferred by treating mice with the tetrapeptide drug SS-31. The interrelationships of mitochondrial ROS and mitochondrial energetics with cell signaling pathways that mediate improved healthspan, including resistance to cardiac hypertrophy and failure, are thus of central interest to the laboratory. As the mTOR pathway is a strong candidate in this linkage, we are also studying the effects of rapamycin and using transgenic mice with altered mTOR signaling to explore this relationship. Evidence from our laboratory indicates that both SS31 and rapamycin can rejuvenate cardiac function in old mice. In addition to physiological and biochemical assays, proteomic and metabolomic technologies are being actively utilized in laboratory studies. Improved cardiac performance in treated old mice is accompanied by remodeling of the proteome towards a more youthful phenotype, including evidence of a reversal of the age-related shift from oxidative to glycolytic metabolism; this is confirmed by metabolomic studies.
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Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research