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Plasma proteomic profile of frailty.
Aging Cell ( IF 8.0 ) Pub Date : 2020-08-06 , DOI: 10.1111/acel.13193 Sanish Sathyan 1 , Emmeline Ayers 1 , Tina Gao 2 , Sofiya Milman 2, 3 , Nir Barzilai 2, 3 , Joe Verghese 1, 2
Aging Cell ( IF 8.0 ) Pub Date : 2020-08-06 , DOI: 10.1111/acel.13193 Sanish Sathyan 1 , Emmeline Ayers 1 , Tina Gao 2 , Sofiya Milman 2, 3 , Nir Barzilai 2, 3 , Joe Verghese 1, 2
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Frailty is a state of decreased physiological reserve and increased vulnerability to adverse outcomes in aging, and is characterized by dysregulation across various biological pathways. Frailty may manifest biologically as alteration in protein expression, possibly regulated at genetic, transcriptional and epigenetic levels. In this study, we examined the proteomic profile associated with frailty defined by an established cumulative frailty index (FI). Using the SomaScan® assay, 4265 proteins were measured in plasma, of which 55 were positively associated and 88 were negatively associated with the FI. The proteins most strongly associated with frailty were fatty acid‐binding proteins, including fatty acid‐binding protein (FABP) (p = 1.96 × 10−19) and FABPA (p = 8.10 × 10−16), leptin (p = 1.43 × 10−14), and ANTR2 (p = 7.95 × 10−20). Pathway analysis with the top 143 frailty‐associated proteins revealed enrichment for proteins in pathways related to lipid metabolism, musculoskeletal development and function, cell‐to‐cell signaling and interaction, cellular assembly, and organization. Frailty prediction model constructed with elastic net regression utilizing 110 proteins demonstrated a correlation between predicted frailty and observed frailty (r = 0.57, p < 2.2 × 10−16). Predicted frailty was also more strongly correlated with chronological age (r = 0.54, p < 2.2 × 10−16) than observed frailty (r = 0.37, p = 1.2 × 10−15). This study identified novel proteins and pathways related to frailty that may offer improved frailty phenotyping and prediction.
中文翻译：
虚弱的血浆蛋白质组学特征。
衰弱是一种生理储备减少和衰老过程中对不良后果的脆弱性增加的状态，其特征是各种生物途径的失调。虚弱可能在生物学上表现为蛋白质表达的改变，可能在遗传、转录和表观遗传水平上受到调节。在这项研究中，我们检查了与由已建立的累积衰弱指数（FI）定义的衰弱相关的蛋白质组谱。使用 SomaScan ®检测，在血浆中测量了 4265 种蛋白质，其中 55 种与 FI 呈正相关，88 种与 FI 呈负相关。与虚弱关系最密切的蛋白质是脂肪酸结合蛋白，包括脂肪酸结合蛋白（FABP）（ p = 1.96 × 10 -19 ）和FABPA（ p = 8.10 × 10 -16 ）、瘦素（ p = 1.43 × 10 −14 ) 和 ANTR2 ( p = 7.95 × 10 −20 )。对前 143 种衰弱相关蛋白的通路分析揭示了与脂质代谢、肌肉骨骼发育和功能、细胞间信号传导和相互作用、细胞组装和组织相关通路中的蛋白质富集。利用 110 个蛋白质通过弹性网络回归构建的衰弱预测模型证明了预测衰弱与观察到的衰弱之间的相关性 ( r = 0.57, p < 2.2 × 10 -16 )。与观察到的虚弱（ r = 0.37， p = 1.2 × 10 -15 ）相比，预测的虚弱与实际年龄的相关性也更强（ r = 0.54， p < 2.2 × 10 -16 ）。 这项研究发现了与虚弱相关的新蛋白质和途径，可以改善虚弱表型和预测。
更新日期：2020-09-24
中文翻译：
虚弱的血浆蛋白质组学特征。
衰弱是一种生理储备减少和衰老过程中对不良后果的脆弱性增加的状态，其特征是各种生物途径的失调。虚弱可能在生物学上表现为蛋白质表达的改变，可能在遗传、转录和表观遗传水平上受到调节。在这项研究中，我们检查了与由已建立的累积衰弱指数（FI）定义的衰弱相关的蛋白质组谱。使用 SomaScan ®检测，在血浆中测量了 4265 种蛋白质，其中 55 种与 FI 呈正相关，88 种与 FI 呈负相关。与虚弱关系最密切的蛋白质是脂肪酸结合蛋白，包括脂肪酸结合蛋白（FABP）（ p = 1.96 × 10 -19 ）和FABPA（ p = 8.10 × 10 -16 ）、瘦素（ p = 1.43 × 10 −14 ) 和 ANTR2 ( p = 7.95 × 10 −20 )。对前 143 种衰弱相关蛋白的通路分析揭示了与脂质代谢、肌肉骨骼发育和功能、细胞间信号传导和相互作用、细胞组装和组织相关通路中的蛋白质富集。利用 110 个蛋白质通过弹性网络回归构建的衰弱预测模型证明了预测衰弱与观察到的衰弱之间的相关性 ( r = 0.57, p < 2.2 × 10 -16 )。与观察到的虚弱（ r = 0.37， p = 1.2 × 10 -15 ）相比，预测的虚弱与实际年龄的相关性也更强（ r = 0.54， p < 2.2 × 10 -16 ）。 这项研究发现了与虚弱相关的新蛋白质和途径，可以改善虚弱表型和预测。
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