Reiter R J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762, USA.
Aging (Milano). 1995 Oct;7(5):340-51. doi: 10.1007/BF03324344.
That free radical destruction of macromolecules is a basis of aging and age-related diseases has considerable experimental support. Melatonin, a hormone produced in organisms as diverse as algae and humans, is believed to have evolved coincident with aerobic metabolism. In all organisms melatonin is produced primarily during the daily period of darkness, with only small amounts being synthesized during the day. In mammals including man, melatonin is produced by and secreted from the pineal gland during the night; however, the night-time production of melatonin falls markedly with aging such that in senescent animals a night-time melatonin rise is barely measurable. This may be significant in terms of aging in the light of recent observations which show that melatonin is a highly efficient free radical scavenger and antioxidant both in vitro and in vivo. In vitro, melatonin has been shown to directly scavenge both the hydroxyl and peroxyl radical, and it does so more efficiently than other known antioxidants. Furthermore, melatonin greatly potentiates the efficiency of previously-discovered endogenous and exogenous antioxidants. In vivo, both physiological and pharmacological levels of melatonin reportedly counteract the devastatingly destructive actions of free radical generating chemicals. For example, melatonin effectively combats DNA damage in rats given massive doses of the chemical carcinogen safrole, and the indole overcomes much of the genomic damage inflicted by ionizing radiation. Also, lipid peroxidation induced by either paraquat, bacterial lipopolysaccharide or H2O2 is highly significantly reduced by concurrent melatonin administration. Finally, cataracts produced in newborn rats by the depletion of the endogenous antioxidant glutathione are prevented by melatonin. These findings provide evidence that melatonin is operative in the cell nucleus, in the aqueous cytosol and in lipid-rich cellular membranes as an antioxidant. Considering this, the loss of this potent antioxidant during aging may be consequential in terms of cellular and organismal aging as well as the onset of age-related diseases. These experimental results from a variety of sources suggest that a more determined approach to the study of melatonin as an anti-aging factor is warranted.
自由基对大分子的破坏是衰老及与年龄相关疾病的基础，这一观点有大量实验依据。褪黑素是一种在从藻类到人类等多种生物中产生的激素，据信它是与有氧代谢同时进化而来的。在所有生物中，褪黑素主要在每日的黑暗时段产生，白天仅合成少量。在包括人类在内的哺乳动物中，褪黑素在夜间由松果体产生并分泌；然而，随着衰老，褪黑素的夜间分泌量显著下降，以至于在衰老动物中，夜间褪黑素的升高几乎无法测量。鉴于最近的观察结果表明褪黑素在体外和体内都是一种高效的自由基清除剂和抗氧化剂，这一点对于衰老可能具有重要意义。在体外，褪黑素已被证明能直接清除羟基自由基和过氧自由基，而且它比其他已知的抗氧化剂更有效地做到这一点。此外，褪黑素极大地增强了先前发现的内源性和外源性抗氧化剂的功效。在体内，据报道褪黑素的生理和药理水平都能抵消自由基生成化学物质的极具破坏性的作用。例如，褪黑素能有效对抗给予大剂量化学致癌物黄樟素的大鼠的DNA损伤，并且这种吲哚能克服电离辐射造成的许多基因组损伤。同样，同时给予褪黑素能显著降低由百草枯、细菌脂多糖或过氧化氢诱导的脂质过氧化。最后，褪黑素可预防新生大鼠因内源性抗氧化剂谷胱甘肽耗竭而产生的白内障。这些发现证明褪黑素作为一种抗氧化剂在细胞核、水性细胞质溶胶和富含脂质的细胞膜中都有作用。考虑到这一点，在衰老过程中这种强效抗氧化剂的丧失对于细胞和机体衰老以及与年龄相关疾病的发生可能是至关重要的。来自各种来源的这些实验结果表明，有必要采取更坚定的方法来研究褪黑素作为一种抗衰老因子。
