Beta-Guanidinopropionic acid as an Intervention Targeting Health-span
Description: There is a general consensus that the basic biology of aging can be modulated to delay not only the aging process per se but also the development and progression of age-related diseases. Based on this, there is increasing focus on the study of interventions that target aging as a means to improve health in the aged population. The goal of this proposal is to provide exceptional training in the basic biology of aging through a research project that may ultimately provide translational benefit to aging humans. As a host institution, the Barshop Institute at UT Health San Antonio provides a world-class scientific community of researchers in the biology of aging. For this proposal, the sponsor Dr. Adam Salmon will provide research training and career mentoring. Dr. Salmon's NIA-funded research focuses on understanding how interventions targeting the aging process can be used to preserve metabolic function in aging and thus is an ideal home for the proposed project. It is well understood that changes in mitochondrial function are a hallmark of aging and play significant roles in age related declines in tissue function and development of age related diseases. In this proposal, we test whether Beta-Guanidinopropionic acid (GPA) might alter mitochondrial energetics to delay or prevent the onset of age related pathologies. Previous studies have suggested that GPA can improve glucose metabolism and exercise endurance in young rodents as well as promote mitochondrial biogenesis. These outcomes seem to be partially mediated by activation of AMP-activated protein kinase (AMPK) signaling. However, there is still a significant knowledge gap regarding intervention with GPA on the physiological decline with age that contributes to animal healthspan. We therefore hypothesize that GPA will reduce age-related physiological declines in function by altering mitochondrial energetics to preserve cellular function. We test this hypothesis using genetically heterogeneous mice (HET3) treated either early or late in life with 1% GPA. Our aims will clarify age related effects on mitochondrial function, tissue homeostasis, and cellular senescence as mediators of the aging process and how they are altered by GPA. We expect this project will not only clarify the potential that GPA has in preserving physiological function during aging, but will also foster the development of skills required to become an independent researcher in the biology of aging.
Funder: American Heart Association
Amount: $53,690
Funding type: training
Funder scheme: Predoctoral Fellowship
Start date: 2019-05-01
End date: 2021-04-30
Investigators: Jonathan Dorigatti, Jonathan Dorigatti
Institution: The University of Texas Health Science Center at San Antonio
Funded outputs count: 2
Funder award ID: 19PRE34450033
OpenAlex ID: G4311463580