This project seeks to identify a central factor driving aging in order to develop targeted interventions to delay the onset or even reverse aging-related pathologies. My preliminary data demonstrate caloric restriction (CR), a proven intervention for increasing lifespan stimulates endogenous production of hydrogen sulfide gas and this is necessary for the stress resistance benefits of CR. Here, we test age related decline of endogenous hydrogen sulfide production and if it is delayed by a specific and more clinically favorable form of dietary restriction, methionine restriction, as a means to increase metabolic fitness, stress resistance and longevity.

Public Health Relevance

This project seeks to identify a central factor driving aging in order to develop targeted interventions to delay the onset or even reverse aging-related pathologies. My preliminary data demonstrate caloric restriction (CR), a proven intervention for increasing lifespan, stimulates endogenous production of hydrogen sulfide gas and this is necessary for the stress resistance benefits of CR. Here, we test age related decline of endogenous hydrogen sulfide production and if it is delayed by a specific and more clinically favorable form of dietary restriction, methionine restriction, as a means to increase metabolic fitness, stress resistance and longevity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Transition Award (R00)
Project #
5R00AG050777-04
Application #
9461455
Study Section
Special Emphasis Panel (NSS)
Program Officer
Fridell, Yih-Woei
Project Start
2017-04-01
Project End
2020-03-31
Budget Start
2018-04-15
Budget End
2019-03-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Hine, Christopher; Mitchell, James R (2017) Endpoint or Kinetic Measurement of Hydrogen Sulfide Production Capacity in Tissue Extracts. Bio Protoc 7:
Nikonorova, Inna A; Al-Baghdadi, Rana J T; Mirek, Emily T et al. (2017) Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice. J Biol Chem 292:6786-6798
Hine, Christopher; Kim, Hyo-Jeong; Zhu, Yan et al. (2017) Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production. Cell Metab 25:1320-1333.e5