褪黑激素和衰老理论：褪黑激素在抗衰老机制中的作用的重要评价。,Journal of Pineal Research

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褪黑激素和衰老理论：褪黑激素在抗衰老机制中的作用的重要评价。
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2013-10-12 , DOI: 10.1111/jpi.12090
Rüdiger Hardeland ₁

Affiliation

经典的衰老理论，例如自由基理论（包括与线粒体有关的理论），主要集中在一些特定的衰老过程上。同时，在以前认为或多或少独立进行的与年龄相关的变化之间，许多互连变得显而易见。自由基增加的损伤不仅与线粒体功能受损有关，而且与免疫重塑过程中发生的发炎有关，还与从具有衰老相关分泌表型（SASP）的有丝分裂阻滞的，DNA损伤的细胞释放促炎细胞因子有关。。SASP可以在干细胞中引起突变，从而降低组织再生的能力，或者在最坏的情况下导致癌症干细胞。氧化应激也已显示可促进端粒磨损。此外，自由基的损害与昼夜节律的减弱有关。细胞振荡器和代谢感应之间存在另一个联系，特别是衰老抑制剂SIRT1，后者充当辅助时钟蛋白。褪黑激素是一种高度多效的调节分子，可与上述所有过程直接或间接相互作用。对这些影响进行了严格审查，重点是衰老的生物体和衰老加速动物的数据。根据在衰老生物体中获得的证据，讨论了在非老年医学背景下或在肿瘤与非肿瘤细胞比较中获得的有时引起争议的发现。尽管在哺乳动物中，很少以完全结论性的方式记录褪黑激素延长生命的过程，

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Melatonin and the theories of aging: a critical appraisal of melatonin's role in antiaging mechanisms.

The classic theories of aging such as the free radical theory, including its mitochondria-related versions, have largely focused on a few specific processes of senescence. Meanwhile, numerous interconnections have become apparent between age-dependent changes previously thought to proceed more or less independently. Increased damage by free radicals is not only linked to impairments of mitochondrial function, but also to inflammaging as it occurs during immune remodeling and by release of proinflammatory cytokines from mitotically arrested, DNA-damaged cells that exhibit the senescence-associated secretory phenotype (SASP). Among other effects, SASP can cause mutations in stem cells that reduce the capacity for tissue regeneration or, in worst case, lead to cancer stem cells. Oxidative stress has also been shown to promote telomere attrition. Moreover, damage by free radicals is connected to impaired circadian rhythmicity. Another nexus exists between cellular oscillators and metabolic sensing, in particular to the aging-suppressor SIRT1, which acts as an accessory clock protein. Melatonin, being a highly pleiotropic regulator molecule, interacts directly or indirectly with all the processes mentioned. These influences are critically reviewed, with emphasis on data from aged organisms and senescence-accelerated animals. The sometimes-controversial findings obtained either in a nongerontological context or in comparisons of tumor with nontumor cells are discussed in light of evidence obtained in senescent organisms. Although, in mammals, lifetime extension by melatonin has been rarely documented in a fully conclusive way, a support of healthy aging has been observed in rodents and is highly likely in humans.

更新日期：2013-09-23

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