Longitudinal Study Section, Translational Gerontology Branch, NIA, NIH, Baltimore, Maryland.
Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, Maryland.
Aging Cell. 2018 Oct;17(5):e12799. doi: 10.1111/acel.12799. Epub 2018 Jul 11.
To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22-93 years old, who were disease- and treatment-free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10 ). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age-associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.
为了描绘出时间年龄的蛋白质组学特征，我们使用 SOMAscan 检测法（SomaLogic，博尔德，科罗拉多州，美国）对 240 名健康的男性和女性（22-93 岁）的血浆进行了 1301 种蛋白质的测量。这些人没有身体和认知上的损伤，没有患任何疾病，也没有接受任何治疗。使用 p ≤ 3.83×10 的显著性阈值，我们发现有 197 种蛋白质与年龄呈正相关，20 种蛋白质与年龄呈负相关。生长分化因子 15（GDF15）与年龄的正相关性最强（GDF15；0.018 ± 0.001，p = 7.49×10）。在我们的样本中，GDF15 与其他心血管风险因素（如胆固醇或炎症标志物）无关。与 217 种与年龄相关的蛋白质相关的功能途径包括血液凝固、趋化因子和炎症途径、轴突导向、肽酶活性和细胞凋亡。通过弹性网络回归模型，我们根据与时间年龄高度相关的 76 种蛋白质的相对浓度创建了一个年龄的蛋白质组学特征（r = 0.94）。我们的发现需要在独立的队列中进行复制，以验证其普遍性。
