Organismal Proteostasis: Collapse in Aging and Rejuvenation Approaches

Prof Richard Morimoto; Northwestern University

 

Rick Morimoto is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research in the Department of Molecular Biosciences at Northwestern University. He was trained in the Department of Biochemistry and Molecular Biology at Harvard University, received the Ph.D. in Molecular Biology from The University of Chicago and undergraduate degree in Biology from the University of Illinois in Chicago. His research is broadly on the biology of aging and risk for a large class of protein conformational diseases. These include Alzheimer’s disease, Frontal Temporal Dementia, Parkinson’s Disease, ALS and Traumatic Brain Encephalopathy all of which cause profound molecular damage to the proteome and accumulation of misfolded and aggregated proteins associated with neuronal dysfunction. Dr. Morimoto's laboratory has published over 300 papers including three monographs and four books and has received multiple ten year MERIT award grants from the NIH. He is an elected member of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and received the Ordre des Palmes Académiques – Commandeur from the French Ministry of Education, the Fyodor Lynen Medal from the German Society of Biochemistry and Molecular Biology, Fellow of the Japanese Society for the Promotion of Science and the Royal Society Wolfson Fellowship at the University of Cambridge. He was a founder of Proteostasis Therapeutics, Inc. to discover small molecule therapeutics for diseases of protein conformation.

Organismal Proteostasis: Collapse in Aging and Rejuvenation Approaches Rick Morimoto Department of Molecular Biosciences, Rice Institute of Biomedical Research, Northwestern University, Evanston, IL 60201 Proteostasis enables the functional health of the proteome by the dynamic properties of the Proteostasis Network (PN) to ensure that protein synthesis, folding and assembly, localization and degradation are robust and resilient. In metazoans, proteostasis is regulated by intertissue communication from sensory neurons to the soma through neuropeptides that regulate the systemic response to heat shock and organismal proteostasis. However, in aging PN capacity declines and represents a primary risk factor for all degenerative diseases. A major contributing factor to the loss of resilience is increased proteome instability which in C. elegans occurs early in adulthood programmed by an epigenetic switch from germline stem cells to somatic tissues at the onset of reproductive maturity. This results in the simultaneous decline of multiple essential adaptive cell stress responses which compromises stress resilience and PN capacity in aging. Our current efforts are to identify the earliest events of aging that predict subsequent tissue and organismal failure of proteostasis and strategies to rejuvenate the PN for health aging.