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Departments of 1 Physiology
2 Cellular and Structural Biology, and the
3 Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio.
4 Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio.
5 Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, Tennessee.
Address correspondence to Walter F. Ward, PhD, Department of Physiology–MSC-7756, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: wardw{at}uthscsa.edu
The free radical theory of aging proposes that the accumulation of oxidative damage is a key component of the aging process. The discovery of F2-isoprostanes (F2-isoPs) and their establishment as a sensitive and accurate biomarker of lipid peroxidation represents a major advance for measuring the oxidative stress status of an organism. We have shown that plasma free and total (free plus esterified) F2-isoPs increase with age (185% and 66%, respectively), and that these increases are reduced by life-extending caloric restriction (50% and 23%, respectively). In addition, we found that levels of esterified F2-isoPs increase 68% with age in liver, and 76% with age in kidney. Caloric restriction modulated the age-related increase, reducing the esterified F2-isoPs levels 27% in liver and 35% in kidney. These age-related increases in esterified F2-isoPs levels correlate well with DNA oxidation, as measured by 8-oxodeoxyguanosine production demonstrating that F2-isoPs are an excellent biomarker for age-related changes in oxidative damage to membranes.
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