Ward Walter F, Qi Wenbo, Van Remmen Holly, Zackert William E, Roberts L Jackson, Richardson Arlan
Department of Physiology-MSC-7756, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.
J Gerontol A Biol Sci Med Sci. 2005 Jul;60(7):847-51. doi: 10.1093/gerona/60.7.847.
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.
衰老的自由基理论认为，氧化损伤的积累是衰老过程的关键组成部分。F2-异前列腺素（F2-isoPs）的发现及其作为脂质过氧化敏感且准确生物标志物的确立，是衡量生物体氧化应激状态的一项重大进展。我们已经表明，血浆游离和总（游离加酯化）F2-异前列腺素会随着年龄增长而增加（分别增加185%和66%），并且这些增加会因延长寿命的热量限制而减少（分别减少50%和23%）。此外，我们发现肝脏中酯化F2-异前列腺素的水平随年龄增长增加68%，肾脏中随年龄增长增加76%。热量限制调节了与年龄相关的增加，使肝脏中酯化F2-异前列腺素水平降低27%，肾脏中降低35%。这些与年龄相关的酯化F2-异前列腺素水平增加与DNA氧化密切相关，通过8-氧代脱氧鸟苷生成来衡量，这表明F2-异前列腺素是膜氧化损伤与年龄相关变化的优秀生物标志物。
