Menni Cristina, Kiddle Steven J, Mangino Massimo, Viñuela Ana, Psatha Maria, Steves Claire, Sattlecker Martina, Buil Alfonso, Newhouse Stephen, Nelson Sally, Williams Stephen, Voyle Nicola, Soininen Hilkka, Kloszewska Iwona, Mecocci Patrizia, Tsolaki Magda, Vellas Bruno, Lovestone Simon, Spector Tim D, Dobson Richard, Valdes Ana M
Department of Twin Research and Genetic Epidemiology, King's College London.
Institute of Psychiatry, King's College London. Medical Research Council Social, Genetic and Developmental Psychiatry Centre, King's College London.
J Gerontol A Biol Sci Med Sci. 2015 Jul;70(7):809-16. doi: 10.1093/gerona/glu121. Epub 2014 Aug 14.
To elucidate the proteomic features of aging in plasma, the subproteome targeted by the SOMAscan assay was profiled in blood samples from 202 females from the TwinsUK cohort. Findings were replicated in 677 independent individuals from the AddNeuroMed, Alzheimer's Research UK, and Dementia Case Registry cohorts. Results were further validated using RNAseq data from whole blood in TwinsUK and the most significant proteins were tested for association with aging-related phenotypes after adjustment for age. Eleven proteins were associated with chronological age and were replicated at protein level in an independent population. These were further investigated at gene expression level in 384 females from the TwinsUK cohort. The two most strongly associated proteins were chordin-like protein 1 (meta-analysis β [SE] = 0.013 [0.001], p = 3.66 × 10(-46)) and pleiotrophin (0.012 [0.005], p = 3.88 × 10(-41)). Chordin-like protein 1 was also significantly correlated with birthweight (0.06 [0.02], p = 0.005) and with the individual Framingham 10-years cardiovascular risk scores in TwinsUK (0.71 [0.18], p = 9.9 × 10(-5)). Pleiotrophin is a secreted growth factor with a plethora of functions in multiple tissues and known to be a marker for cardiovascular risk and osteoporosis. Our study highlights the importance of proteomics to identify some molecular mechanisms involved in human health and aging.
为了阐明血浆中衰老的蛋白质组学特征，在来自TwinsUK队列的202名女性的血液样本中，对SOMAscan分析所靶向的亚蛋白质组进行了分析。研究结果在来自AddNeuroMed、英国阿尔茨海默病研究和痴呆症病例登记队列的677名独立个体中得到了重复验证。使用TwinsUK全血的RNAseq数据进一步验证了结果，并在调整年龄后，对最显著的蛋白质进行了与衰老相关表型关联的测试。11种蛋白质与实际年龄相关，并在独立人群中得到了蛋白质水平的重复验证。在来自TwinsUK队列的384名女性中，对这些蛋白质在基因表达水平上进行了进一步研究。两种相关性最强的蛋白质是类脊索蛋白1（荟萃分析β[标准误]=0.013[0.001]，p=3.66×10⁻⁴⁶）和多效生长因子（0.012[0.005]，p=3.88×10⁻⁴¹）。类脊索蛋白1还与出生体重显著相关（0.06[0.02]，p=0.005），并且与TwinsUK中个体的弗雷明汉10年心血管风险评分相关（0.71[0.18]，p=9.9×10⁻⁵）。多效生长因子是一种分泌型生长因子，在多个组织中具有多种功能，并且已知是心血管风险和骨质疏松症的标志物。我们的研究强调了蛋白质组学在识别参与人类健康和衰老的一些分子机制方面的重要性。
