Role of Longevity Regulatory Pathways in Age-dependent Macro-molecular Damage in Yeast The identification of the genes and pathways that regulate the life span in simple model organisms has been invaluable to the initial understanding of the mechanisms of aging in mammals. The systems biology and genetics studies proposed in this application will help define the role of various signal transduction genes and pathways in the regulation of aging and resistance to the damage caused by various stresses in the unicellular eukaryote S. cerevisiae. These pathways are centered around the Ras and Sch9 proteins, which are conserved from yeast to humans, and are implicated in cancer and other diseases. The proposed studies will: 1) shed light on the fundamental molecular mechanisms responsible for the effects of previously identified pro-aging genes including RAS2 and SCH9, 2) investigate novel molecules, genes, and pathways that affect aging and resistance to damage and that may be conserved from yeast to humans, 3) develop a novel paradigm to study aging, that is simpler and more directly relevant to aging in mammals, 4) investigate the anti-aging molecular mechanisms of calorie restriction, which appear to be conserved from yeast to mammals. The proposed studies will contribute to the description of the fundamental mechanisms of aging and also to the identification of novel genes and pathways that can protect against human diseases.

Public Health Relevance

We propose to study the age-dependent macro-molecular damage in yeast. The studies proposed in this application will help elucidate the complex relationship between nutrients, conserved pro- aging signaling pathways, oxidative stress, DNA mutagenesis and protein homeostasis, and mitochondrial function during aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG020642-12
Application #
8663147
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Guo, Max
Project Start
2002-04-01
Project End
2018-05-31
Budget Start
2014-07-15
Budget End
2015-05-31
Support Year
12
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Other Specialized Schools
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Brandhorst, Sebastian; Choi, In Young; Wei, Min et al. (2015) A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab 22:86-99

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