Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging.
The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and alpha-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (alpha-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress.
Hyun
Dong-Hoon
DH
Laboratory of Neurosciences and Laboratory of Experimental Gerontology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Emerson
Scott S
SS
Jo
Dong-Gyu
DG
Mattson
Mark P
MP
de Cabo
Rafael
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D031204:Caloric Restriction; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D024502:alpha-Tocopherol