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Northwestern receives $32.4 million to study healthy aging

Focus is on molecular biology and role of proteins in disease and life span
morimoto hevolution proteins
Richard Morimoto works with a postdoctoral fellow in his lab’s cell culture room. Credit: Monika Wnuk

Northwestern University has been awarded $32.4 million over five years from the Hevolution Foundation to study proteostasis — the processes by which cells maintain protein health for good overall health and to prevent diseases of protein misfolding. A key goal is to improve the health people experience as they age, particularly in their final years.

The research focuses on defining healthy proteostasis in human cells and identifying ways to maintain proteostasis in a robust, resilient state. This work will increase understanding of the underlying causes of aging and help prevent rather than treat the diseases of old age.

“We are thrilled that the Proteostasis Consortium is partnering with the Hevolution Foundation to address this fundamental question on the biology of aging,” said Richard I. Morimoto, the principal investigator on the grant. “Our team is working to provide new insights on the molecular biology of healthy aging and develop approaches to rejuvenate cellular and organismal health.”

Morimoto is an expert on the cellular response to damaged proteins. He is the Bill and Gayle Cook Professor of Biology and director of the Rice Institute for Biomedical Research in Northwestern’s Weinberg College of Arts and Sciences.

The new study is part of the growing field of geroscience, which seeks to understand the genetic, molecular and cellular mechanisms that make aging a major risk factor and driver of common chronic conditions and diseases of older people.

The Proteostasis Consortium is a group of investigators who have worked together on proteostasis in biology, health and diseases. In addition to Northwestern, members are from the University of California San Francisco, the Gladstone Institute of Neurological Disease, Stanford University, Scripps Research, Harvard Medical School and the Health Research Institute of Asturias (ISPA) in Spain. There is a co-principal investigator from each institution on the grant.

“This innovative work promises to advance our understanding of aging and longevity and substantially contributes to Northwestern's extensive research portfolio in those areas.”
— Eric Perreault, vice president for research

The team will provide a detailed molecular description of healthy aging through the lens of proteostasis. The researchers believe that in healthy aging the accumulation of misfolded proteins are kept in check by the robustness and capacity of the proteostasis network. This network guides the proper synthesis, folding and assembly, and degradation of each component of the proteome.

There is emerging evidence that aging causes a decline in one or more of the proteostasis network components leading to the accumulation of damaged, misfolded and aggregated proteins. This piling up of proteins interferes with the integrity of cellular machinery, thus compromising healthy aging and increasing the risk for diseases of protein conformation including Alzheimer’s and Parkinson’s diseases, cancers and metabolic diseases.

The mechanistic insights from various components of the research will guide the development of new measures of health and predictors of disease as well as new targets for pharmacological approaches to stably rebalance protein folding and degradation in aging.

“Rick Morimoto’s record of high-impact research continues to help drive Northwestern's excellence in the biosciences — one of our University priorities,” said Eric Perreault, Northwestern’s vice president for research. “His latest project exemplifies this commitment by addressing the critical link between aging and proteostasis dysfunction. This innovative work promises to advance our understanding of aging and longevity and substantially contributes to Northwestern's extensive research portfolio in those areas.

Morimoto’s group at Northwestern identified the human heat shock genes that function as molecular chaperones in protein folding and the stress-signaling pathways that regulate the heat shock response. The researchers developed C. elegans models for neurodegenerative diseases and used these models to identify molecular events in aging that increase the risk for protein misfolding diseases. (C. elegans is a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome is known.)

The Hevolution Foundation, established in 2021, is a global nonprofit organization that provides grants and early-stage investments to incentivize research and entrepreneurship in health span science.