The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms
The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms
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DOI：
10.1007/s11357-008-9058-z
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发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Mele, James
中科院分区：
文献类型：
--
作者：
Buffenstein, Rochelle;Edrey, Yael H.;Mele, James
活性氧（ROS）是有氧代谢不可避免的副产物，已知会对细胞和分子造成氧化损伤。这反过来又被广泛认为是寿命和健康寿命的关键决定因素。虽然在广泛的物种中的研究支持ROS在许多与年龄相关的疾病中的作用，但其在衰老本身中的作用受到质疑。比较数据从广泛的吸热提供模棱两可的支持这一理论，有许多例外和不确定的结果，无论是氧化应激是一个相关的或最大的物种寿命的决定因素。现有数据不支持代谢率和体内活性氧产生是寿命的决定因素，或上级抗氧化防御有助于物种寿命的前提。相反，已发表的研究往往表明，与物种寿命呈负相关或缺乏相关性。此外，许多长寿物种，如鸟类，蝙蝠和鼹鼠，即使在年轻时也表现出高水平的氧化损伤。类似地，改变关键抗氧化剂表达的基因操作不一定会对寿命产生影响，即使氧化损伤水平可能会受到影响。虽然这些对自由基衰老理论的直接预测的多个例外都可能反映了物种特异性的“私人”衰老机制，但相反数据的优势仍然对这一庄严的理论提出了挑战。因此，与公认的教条相反，氧化应激作为长寿的决定因素的作用仍然有待商榷。
Reactive oxygen species (ROS), inevitable byproducts of aerobic metabolism, are known to cause oxidative damage to cells and molecules. This, in turn, is widely accepted as a pivotal determinant of both lifespan and health span. While studies in a wide range of species support the role of ROS in many age-related diseases, its role in aging per se is questioned. Comparative data from a wide range of endotherms offer equivocal support for this theory, with many exceptions and inconclusive findings as to whether or not oxidative stress is either a correlate or a determinant of maximum species lifespan. Available data do not support the premise that metabolic rate and in vivo ROS production are determinants of lifespan, or that superior antioxidant defense contributes to species longevity. Rather, published studies often show either a negative associate or lack of correlation with species longevity. Furthermore, many long-living species such as birds, bats and mole-rats exhibit high levels of oxidative damage even at young ages. Similarly genetic manipulations altering expression of key antioxidants do not necessarily show an impact on lifespan, even though oxidative damage levels may be affected. While it is possible that these multiple exceptions to straightforward predictions of the free radical theory of aging all reflect species-specific, "private" mechanisms of aging, the preponderance of contrary data nevertheless present a challenge to this august theory. Therefore, contrary to accepted dogma, the role of oxidative stress as a determinant of longevity is still open to question.