Abstract

Age-related human diseases including cancer, Alzheimer's and Parkinson's disease show a clear correlation with mitochondrial dysfunction and reactive oxygen species (ROS). We propose to undertake a combined genetic, biochemical and bioenergetics approach to test the hypothesis that mitochondrial dysfunction and particularly mitochondrial reactive oxygen species (ROS) generation are causatively involved in age related disease. We propose to use three main manipulations of mitochondrial features-electron transport chain complexes, the glutathione pool and superoxide levels-and to measure outcomes models of these three age-related conditions. We believe that the proposed Program Project will make a significant contribution to our understanding of how mitochondrial function contributes to age-related disease with a view towards designing successful interventions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG025901-03
Application #
7572836
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2 (O2))
Program Officer
Wise, Bradley C
Project Start
2007-03-01
Project End
2012-02-29
Budget Start
2009-04-01
Budget End
2010-02-28
Support Year
3
Fiscal Year
2009
Total Cost
$1,577,939
Indirect Cost

  Institution

Name
Buck Institute for Age Research
Department
Type
DUNS #
786502351
City
Novato
State
CA
Country
United States
Zip Code
94945

  Publications

Leonoudakis, Dmitri; Rane, Anand; Angeli, Suzanne et al. (2017) Anti-Inflammatory and Neuroprotective Role of Natural Product Securinine in Activated Glial Cells: Implications for Parkinson's Disease. Mediators Inflamm 2017:8302636
Siddiqui, Almas; Rane, Anand; Rajagopalan, Subramanian et al. (2016) Detrimental effects of oxidative losses in parkin activity in a model of sporadic Parkinson's disease are attenuated by restoration of PGC1alpha. Neurobiol Dis 93:115-20
Siddiqui, Almas; Bhaumik, Dipa; Chinta, Shankar J et al. (2015) Mitochondrial Quality Control via the PGC1?-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation But Independently Restored by Rapamycin. J Neurosci 35:12833-44
Chinta, Shankar J; Woods, Georgia; Rane, Anand et al. (2015) Cellular senescence and the aging brain. Exp Gerontol 68:3-7
Velarde, Michael C; Demaria, Marco; Melov, Simon et al. (2015) Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells. Proc Natl Acad Sci U S A 112:10407-12
Laberge, Remi-Martin; Sun, Yu; Orjalo, Arturo V et al. (2015) MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 17:1049-61
Lieu, Christopher A; Dewey, Colleen M; Chinta, Shankar J et al. (2014) Lithium prevents parkinsonian behavioral and striatal phenotypes in an aged parkin mutant transgenic mouse model. Brain Res 1591:111-7
Quinlan, Casey L; Perevoschikova, Irina V; Goncalves, Renata L S et al. (2013) The determination and analysis of site-specific rates of mitochondrial reactive oxygen species production. Methods Enzymol 526:189-217
Chinta, S J; Lieu, C A; Demaria, M et al. (2013) Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease? J Intern Med 273:429-36
Quinlan, Casey L; Perevoshchikova, Irina V; Hey-Mogensen, Martin et al. (2013) Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol 1:304-12

Showing the most recent 10 out of 78 publications