The development of clinical interventions that significantly improve human healthspan requires robust markers of biological age as well as thoughtful therapeutic targets. To promote these goals, we performed a systematic review and analysis of human aging and proteomics studies. The systematic review includes 36 different proteomics analyses, each of which identified proteins that significantly changed with age. We discovered 1,128 proteins that had been reported by at least two or more analyses and 32 proteins that had been reported by five or more analyses. Each of these 32 proteins has known connections relevant to aging and age-related disease. GDF15, for example, extends both lifespan and healthspan when overexpressed in mice and is additionally required for the anti-diabetic drug metformin to exert beneficial effects on body weight and energy balance. Bioinformatic enrichment analyses of our 1,128 commonly identified proteins heavily implicated processes relevant to inflammation, the extracellular matrix, and gene regulation. We additionally propose a novel proteomic aging clock comprised of proteins that were reported to change with age in plasma in three or more different studies. Using a large patient cohort comprised of 3,301 subjects (aged 18–76 years), we demonstrate that this clock is able to accurately predict human age.

要开发能显着改善人类健康水平的临床干预措施，就需要生物年龄的可靠标记以及周到的治疗目标。为了实现这些目标，我们对人类衰老和蛋白质组学研究进行了系统的审查和分析。系统评价包括36种不同的蛋白质组学分析，每种分析都鉴定出随着年龄的增长而发生显着变化的蛋白质。我们发现至少两次或更多次分析报告了1,128个蛋白质，五个或更多次分析报告了32个蛋白质。这32种蛋白质中的每一种都具有与衰老和与年龄相关的疾病有关的已知联系。例如，GDF15，当在小鼠中过度表达时，可延长寿命和健康寿命，而且抗糖尿病药物二甲双胍还需要它才能对体重和能量平衡产生有益作用。我们对1,128种通常鉴定出的蛋白质的生物信息学富集分析与炎症，细胞外基质和基因调控有关，这些过程与基因过程密切相关。我们另外提出了一种新的蛋白质组学老化时钟，该时钟由三种或更多种不同研究中据报道随着血浆中年龄而变化的蛋白质组成。使用由3,301名受试者（年龄18-76岁）组成的大型患者队列，我们​​证明了该时钟能够准确预测人的年龄。和基因调控。我们另外提出了一种新的蛋白质组学老化时钟，该时钟由三种或更多种不同研究中据报道随着血浆中年龄而变化的蛋白质组成。使用由3,301名受试者（年龄18-76岁）组成的大型患者队列，我们​​证明了该时钟能够准确预测人的年龄。和基因调控。我们另外提出了一种新的蛋白质组学老化时钟，该时钟由三种或更多种不同研究中据报道随着血浆中年龄而变化的蛋白质组成。使用由3,301名受试者（年龄18-76岁）组成的大型患者队列，我们​​证明了该时钟能够准确预测人的年龄。