The long-term goal of the parent grant is to understand the functional and structural consequences of oxidation in muscle proteins, in order to illuminate the mechanisms by which oxidative stress affects human health and aging, with the two aims focusing on two key muscle proteins ? calmodulin and myosin. The present administrative supplement extends the second aim, on myosin, to include studies on sex differences in animal models. These studies will focus particular attention on the role of estrogen modulating post-translational modifications of myosin. The high potential impact of this work is made possible by a collaboration with an expert in mouse models of aging, oxidation, and estrogen. Thus this work starts with the novel approaches of muscle biophysics and structural biology in the parent grant, and is augmented by the complementary expertise in muscle physiology and sex differences in the collaborator?s laboratory. This supplemental project offers a unique and innovative combination of approaches, all focused on a timely goal ? to explain how sex hormones, particularly the less studied female sex hormone, impact the complex effects of oxidation and aging on muscle protein function, structure, and dynamics.

Public Health Relevance

This project?s goal is to understand how muscle proteins become damaged by oxidation (the addition of oxygen atoms), which occurs in the processes of aging and degenerative disease. The present proposal focuses on the role of sex differences on the age-related oxidation of myosin. The goal is to aid future efforts to prevent or reverse the effects of aging and degenerative diseases, such as heart failure and muscle weakness.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG026160-15
Application #
9902266
Study Section
Special Emphasis Panel (NSS)
Program Officer
Williams, John
Project Start
2004-09-15
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
15
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biochemistry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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