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老年人的血浆蛋白质组特征与年龄、健康跨度和全因死亡率。

Plasma proteomic profile of age, health span, and all-cause mortality in older adults.

机构信息

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Institute for Aging Research, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.

出版信息

Aging Cell. 2020 Nov;19(11):e13250. doi: 10.1111/acel.13250. Epub 2020 Oct 22.

Abstract

Aging is a complex trait characterized by a diverse spectrum of endophenotypes. By utilizing the SomaScan proteomic platform in 1,025 participants of the LonGenity cohort (age range: 65-95, 55.7% females), we found that 754 of 4,265 proteins were associated with chronological age. Pleiotrophin (PTN; β[SE] = 0.0262 [0.0012]; p = 3.21 × 10 ), WNT1-inducible-signaling pathway protein 2 (WISP-2; β[SE] = 0.0189 [0.0009]; p = 4.60 × 10 ), chordin-like protein 1 (CRDL1; β[SE] = 0.0203[0.0010]; p = 1.45 × 10 ), transgelin (TAGL; β[SE] = 0.0215 [0.0011]; p = 9.70 × 10 ), and R-spondin-1(RSPO1; β[SE] = 0.0208 [0.0011]; p = 1.09 × 10 ), were the proteins most significantly associated with age. Weighted gene co-expression network analysis identified two of nine modules (clusters of highly correlated proteins) to be significantly associated with chronological age and demonstrated that the biology of aging overlapped with complex age-associated diseases and other age-related traits. The correlation between proteomic age prediction based on elastic net regression and chronological age was 0.8 (p < 2.2E-16). Pathway analysis showed that inflammatory response, organismal injury and abnormalities, cell and organismal survival, and death pathways were associated with aging. The present study made novel associations between a number of proteins and aging, constructed a proteomic age model that predicted mortality, and suggested possible proteomic signatures possessed by a cohort enriched for familial exceptional longevity.

摘要

衰老是一种复杂的特征,具有多种表型。利用 LonGenity 队列的 1025 名参与者中的 SomaScan 蛋白质组学平台(年龄范围:65-95 岁,55.7%为女性),我们发现 4265 种蛋白质中的 754 种与实际年龄有关。多效蛋白(PTN;β[SE] = 0.0262 [0.0012];p = 3.21×10)、WNT1 诱导信号通路蛋白 2(WISP-2;β[SE] = 0.0189 [0.0009];p = 4.60×10)、类 Chordin 蛋白 1(CRDL1;β[SE] = 0.0203[0.0010];p = 1.45×10)、转胶蛋白(TAGL;β[SE] = 0.0215 [0.0011];p = 9.70×10)和 R 应答蛋白 1(RSPO1;β[SE] = 0.0208 [0.0011];p = 1.09×10)是与年龄最显著相关的蛋白质。加权基因共表达网络分析确定了 9 个模块(高度相关蛋白质的聚类)中的两个与实际年龄显著相关,并表明衰老的生物学与复杂的年龄相关疾病和其他与年龄相关的特征重叠。基于弹性网络回归的蛋白质组学年龄预测与实际年龄之间的相关性为 0.8(p < 2.2E-16)。途径分析显示,炎症反应、机体损伤和异常、细胞和机体存活以及死亡途径与衰老有关。本研究在多个蛋白质与衰老之间建立了新的关联,构建了预测死亡率的蛋白质组学年龄模型,并提出了可能存在于一个富含家族性长寿的队列中的蛋白质组学特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6e3/7681045/afcfa6d22edd/ACEL-19-e13250-g001.jpg

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