Sirtuins are Not Conserved Longevity Genes.
Sirtuins are Not Conserved Longevity Genes.
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DOI：
10.1093/lifemeta/loac025
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发表时间：
2022-10
期刊：
影响因子：
--
通讯作者：
Brenner, Charles
中科院分区：
文献类型：
--
作者：
Brenner, Charles
序列保守意味着功能保守，这是生物学的核心。动物寿命是所选特征的一种紧急属性，它整合了在生殖成熟后执行身体和心理功能的能力。虽然酵母Sir2基因被认为是基于老年母细胞复制寿命延长而被提名的长寿基因，但这并不是一个被选择的特征：Sir2在时间上的老化是被选择的，并且Sir2在复制寿命中的直接靶标不是保守的。虽然很难想象每500万个酵母细胞中就有一个具有优势的基因如何预测动物衰老的原因，但Sir2同源基因的过度表达在无脊椎动物中进行了长寿测试。由于人工阳性结果在筛选出之前几年就有了报道，而且尚不清楚Sir2在酵母的时间顺序老化和氨基酸缺乏的果蝇中作为促衰老基因发挥作用，全球对长寿表型的追求受到框架偏差、确认偏差和炒作的混合推动。宣传这些偏见的评论文章如此猖獗，以至于很少有研究人员考虑到sirtuin作为长寿基因的证据是多么薄弱。认识到在几千人年和数十亿美元的努力之后，已经确定了sirtuins和寿命之间的一些积极关联，我们回顾了这些数据，并建议拒绝以下观点：1)sirtuins与动物寿命有任何特定的联系；2)sirtuins是NAD补充的有益影响的主要中介。
It is central to biology that sequence conservation suggests functional conservation. Animal longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive maturity. Though the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells, this is not a selected trait: SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not conserved. Though it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals, overexpression of SIR2 homologs was tested in invertebrates for longevity. Because artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation, a global pursuit of longevity phenotypes was driven by a mixture of framing bias, confirmation bias and hype. Review articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity genes. Acknowledging that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort, we review the data and suggest rejection of the notions that sirtuins 1) have any specific connection to lifespan in animals and 2) are primary mediators of the beneficial effects of NAD repletion.
影响因子：
3.7
作者：
Assali DR;Hsu CT;Gunapala KM;Aguayo A;McBurney M;Steele AD
通讯作者：
Steele AD