The main purpose of this study is to determine whether the long-term administration of co-enzyme Q (CoQ) , or ubiquinone, retards or accelerates the aging process in mice and to elucidate the underlying mechanisms. CoQ is present in the hydrophobic interior of virtually all the cellular membranes and has versatile functions. It is best known as a component of the electron transport system in the inner mitochondrial membrane, where, in concert with alpha-tocopherol, it also acts as an antioxidant, inhibiting oxidative damage. Paradoxically, auto-oxidation of CoQ is also the main source of mitochondrial superoxide anion radical and H2O2 generation CoQ is being widely consumed by humans as a dietary supplement, even though the effects of long-term intake of CoQ are virtually unknown. Whether the long-term intake of CoQ leads to an attenuation or an exacerbation of oxidative stress has not been determine. The present study will elucidate the nature of biochemical and behavioral perturbations following the administration of exogenous CoQ10 to mice. The specific hypothesis to be validated or refuted is that """"""""CoQ administration will decrease the level of oxidative stress, improve and preserve mitochondrial respiratory functions, enhance motor and cognitive performance, and extend life span of mice."""""""" Specific Aims include determination of the effects of CoQ administration on: (1) the longevity of mice; (2) age-associated changes in mitochondrial respiratory functions and oxidative damage; (3) perturbations of homeostasis among the main anti-oxidative defenses; (4) age-related accrual of oxidative damage to lipids, proteins and DNA in tissue homogenates; and (5) age-associated decline in cognitive and motor abilities of the mice. Results of this study will provide an understanding of the mechanisms by which CoQ intake may have a beneficial or deleterious effect on the aging process in mice.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG017526-05
Application #
6629864
Study Section
Special Emphasis Panel (ZRG1-OBM-2 (01))
Program Officer
Finkelstein, David B
Project Start
2000-03-01
Project End
2005-05-31
Budget Start
2003-06-15
Budget End
2004-05-31
Support Year
5
Fiscal Year
2003
Total Cost
$329,211
Indirect Cost
Name
University of Southern California
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Orr, William C; Radyuk, Svetlana N; Sohal, Rajindar S (2013) Involvement of redox state in the aging of Drosophila melanogaster. Antioxid Redox Signal 19:788-803
Sohal, Rajindar S; Orr, William C (2012) The redox stress hypothesis of aging. Free Radic Biol Med 52:539-555
Sumien, Nathalie; Heinrich, Kevin R; Shetty, Ritu A et al. (2009) Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr 139:1926-32
Sohal, Rajindar S; Forster, Michael J (2007) Coenzyme Q, oxidative stress and aging. Mitochondrion 7 Suppl:S103-11
Sohal, Rajindar S; Kamzalov, Sergey; Sumien, Nathalie et al. (2006) Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice. Free Radic Biol Med 40:480-7
McDonald, Shelley R; Sohal, Rajindar S; Forster, Michael J (2005) Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med 38:729-36
Kamzalov, Sergey; Sohal, Rajindar S (2004) Effect of age and caloric restriction on coenzyme Q and alpha-tocopherol levels in the rat. Exp Gerontol 39:1199-205
Sumien, Nathalie; Heinrich, Kevin R; Sohal, Rajindar S et al. (2004) Short-term vitamin E intake fails to improve cognitive or psychomotor performance of aged mice. Free Radic Biol Med 36:1424-33
Kamzalov, Sergey; Sumien, Nathalie; Forster, Michael J et al. (2003) Coenzyme Q intake elevates the mitochondrial and tissue levels of Coenzyme Q and alpha-tocopherol in young mice. J Nutr 133:3175-80
Kwong, Linda K; Kamzalov, Sergey; Rebrin, Igor et al. (2002) Effects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radic Biol Med 33:627-38