Department of Food Science, Nutrition and Health Promotion, Mississippi State University, MS 39762, USA.
USDA, Agricultural Research Service, Grand Forks Human Nutrition Center, Grand Forks, ND 58202, USA.
Free Radic Biol Med. 2018 Nov 1;127:3-13. doi: 10.1016/j.freeradbiomed.2018.05.067. Epub 2018 May 18.
Accumulation of genome and macromolecule damage is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although processes of aging are irreversible, they can be modulated by genome maintenance pathways and environmental factors such as diet. Selenium (Se) confers its physiological functions mainly through selenoproteins, but Se compounds and other proteins that incorporate Se nonspecifically also impact optimal health. Bruce Ames proposed that the aging process could be mitigated by a subset of low-hierarchy selenoproteins whose levels are preferentially reduced in response to Se deficiency. Consistent with this notion, results from two selenotranscriptomic studies collectively implicate three low-hierarchy selenoproteins in age or senescence. Experimental evidence generally supports beneficial roles of selenoproteins in the protection against damage accumulation and redox imbalance, but some selenoproteins have also been reported to unexpectedly display harmful functions under sporadic conditions. While longevity and healthspan are usually thought to be projected in parallel, emerging evidence suggests a trade-off between longevity promotion and healthspan deterioration with damage accumulation. We propose that longevity promotion under conditions of Se deficiency may be attributed to 1) stress-response hormesis, an advantageous event of resistance to toxic chemicals at low doses; 2) reduced expression of selenoproteins with paradoxical functions to a lesser extent. In particular, selenoprotein H is an evolutionally conserved nuclear selenoprotein postulated to confer Se functions in redox regulation, genome maintenance, and senescence. This review highlights the need to pinpoint roles of specific selenoproteins and Se compounds in healthspan and lifespan for a better understanding of Se contribution at nutritional levels of intake to healthy aging.
基因组和大分子损伤的积累是衰老、与年龄相关的退行性变和基因组不稳定性综合征的标志。虽然衰老过程是不可逆转的，但它们可以通过基因组维护途径和环境因素（如饮食）来调节。硒（Se）主要通过硒蛋白发挥其生理功能，但 Se 化合物和其他非特异性掺入 Se 的蛋白质也会影响最佳健康。Bruce Ames 提出，衰老过程可以通过一组低层次的硒蛋白来缓解，这些硒蛋白的水平在 Se 缺乏时优先降低。这一观点得到了两项硒转录组学研究的结果的支持，这些研究共同表明三种低层次的硒蛋白与年龄或衰老有关。实验证据普遍支持硒蛋白在防止损伤积累和氧化还原失衡方面的有益作用，但也有报道称一些硒蛋白在偶发条件下会表现出意想不到的有害功能。虽然长寿和健康寿命通常被认为是平行的，但新出现的证据表明，随着损伤积累，长寿促进和健康寿命恶化之间存在权衡。我们提出，在 Se 缺乏的情况下促进长寿可能归因于 1）应激反应的兴奋效应，即在低剂量下抵抗有毒化学物质的有利事件；2）表达水平降低，具有矛盾功能的硒蛋白表达程度较低。特别是，硒蛋白 H 是一种进化上保守的核硒蛋白，据推测它在氧化还原调节、基因组维护和衰老中赋予 Se 功能。这篇综述强调了需要确定特定硒蛋白和 Se 化合物在健康寿命和寿命中的作用，以更好地理解 Se 在营养摄入水平上对健康衰老的贡献。
