Mammalian species differ up to 100-fold in their aging rates and maximum lifespans. Long-lived mammals appear to possess traits that extend lifespan and healthspan. Genomic analyses have not revealed a single pro-longevity function that would account for all longevity effects. In contrast, it appears that pro-longevity mechanisms may be complex traits afforded by connections between metabolism and protein functions that are impossible to predict by genomic approaches alone. Thus, metabolomics and proteomics studies will be required to understand the mechanisms of longevity. Several examples are reviewed that demonstrate the naked mole rat (NMR) shows unique proteomic signatures that contribute to longevity by overcoming several hallmarks of aging. SIRT6 is also discussed as an example of a protein that evolves enhanced enzymatic function in long-lived species. Finally, it is shown that several longevity-related proteins such as Cip1/p21, FOXO3, TOP2A, AKT1, RICTOR, INSR, and SIRT6 harbor posttranslational modification (PTM) sites that preferentially appear in either short- or long-lived species and provide examples of crosstalk between PTM sites. Prospects of enhancing lifespan and healthspan of humans by altering metabolism and proteoforms with drugs that mimic changes observed in long-lived species are discussed.

中文翻译：

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长寿哺乳动物的蛋白质组学。

哺乳动物物种的衰老速度和最长寿命相差多达 100 倍。长寿的哺乳动物似乎具有延长寿命和健康寿命的特征。基因组分析尚未揭示出可以解释所有长寿效应的单一长寿功能。相比之下，长寿机制似乎可能是由代谢和蛋白质功能之间的联系所提供的复杂特征，而仅通过基因组方法无法预测这些特征。因此，需要代谢组学和蛋白质组学研究来了解长寿的机制。回顾了几个例子，证明裸鼹鼠 (NMR) 显示出独特的蛋白质组特征，这些特征通过克服衰老的几个特征而有助于长寿。SIRT6 也被作为在长寿物种中进化增强酶功能的蛋白质的一个例子进行讨论。最后，研究表明，一些长寿相关蛋白，如 Cip1/p21、FOXO3、TOP2A、AKT1、RICTOR、INSR 和 SIRT6 含有翻译后修饰 (PTM) 位点，这些位点优先出现在短寿命或长寿命物种中，并提供PTM 站点之间串扰的示例。讨论了通过使用模仿长寿物种中观察到的变化的药物来改变新陈代谢和蛋白质形式来延长人类寿命和健康寿命的前景。