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Proteomics Analysis to Identify and Characterize the Biomarkers and Physical Activities of Non-Frail and Frail Older Adults

机译:蛋白质组学分析以鉴定和表征非脆弱和脆弱老年人的生物标记和体育活动

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摘要

Globally, the proportion of older adults is increasing. Older people face chronic conditions such as sarcopenia and functional decline, which are often associated with disability and frailty. Proteomics assay of potential serum biomarkers of frailty in older adults. Older adults were divided into non-frail and frail groups (n = 6 each; 3 males in each group) in accordance with the Chinese-Canadian Study of Health and Aging Clinical Frailty Scale. Adults were measured for grip power and the 6-min walk test for physical activity, and venous blood was sampled after adults fasted for 8 h. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used for proteomics assay. The groups were compared for levels of biomarkers by t test and Pearson correlation analysis. Non-frail and frail subjects had mean age 77.5±0.4 and 77.7±1.6 years, mean height 160.5±1.3 and 156.6±2.9 cm and mean weight 62.5±1.2 and 62.8±2.9 kg, respectively. Physical activity level was lower for frail than non-frail subjects (grip power: 13.8±0.4 vs 26.1±1.2 kg; 6-min walk test: 215.2±17.2 vs 438.3±17.2 m). Among 226 proteins detected, for 31, serum levels were significantly higher for frail than non-frail subjects; serum levels of Ig kappa chain V-III region WOL, COX7A2, and albumin were lower. The serum levels of ANGT, KG and AT were 2.05-, 1.76- and 2.22-fold lower (all p < 0.05; Figure 1A, 2A and 3A) for non-frail than frail subjects and were highly correlated with grip power (Figure 1B, 2B and 3B). Our study found that ANGT, KG and AT levels are known to increase with aging, so degenerated vascular function might be associated with frailty. In total, 226 proteins were revealed proteomics assay; levels of angiotensinogen (ANGT), kininogen-1 (KG) and antithrombin III (AT) were higher in frail than non-frail subjects (11.26±2.21 vs 5.09±0.74; 18.42±1.36 vs 11.64±1.36; 22.23±1.64 vs 9.52±0.95, respectively, p < 0.05). These 3 factors were highly correlated with grip power (p < 0.05), with higher correlations between grip power and serum levels of ANGT (r = -0.89), KG (r = -0.90), and AT (r = -0.84). In conclusion, this is the first study to demonstrate a serum proteomic profile characteristic of frailty in older adults. Serum ANGT, KG and AT levels could be potential biomarkers for monitoring the development and progression of frailty in older adults.
机译:在全球范围内,老年人的比例正在增加。老年人面临诸如肌肉减少症和功能衰退等慢性疾病,这些疾病通常与残疾和虚弱相关。蛋白质组学测定老年人脆弱的潜在血清生物标志物。根据中国-加拿大健康和衰老临床脆弱性研究量表,将老年人分为虚弱和虚弱的组(每组n = 6;每组3男性)。测量成年人的抓地力和6分钟步行测试的体力活动,并在成年人禁食8小时后取样静脉血。超高效液相色谱-串联质谱用于蛋白质组学分析。通过t检验和Pearson相关分析比较各组的生物标志物水平。非体弱和体弱的受试者的平均年龄分别为77.5±0.4和77.7±1.6岁,平均身高160.5±1.3和156.6±2.9 cm,平均体重为62.5±1.2和62.8±2.9 kg。体弱者的体力活动水平低于非体弱者(握力:13.8±0.4 vs 26.1±1.2 kg; 6分钟步行测试:215.2±17.2 vs 438.3±17.2 m)。在检测到的226种蛋白质中,有31种的脆弱人群血清水平明显高于非脆弱人群。血清Igκ链V-III区的WOL,COX7A2和白蛋白水平较低。非体弱的人的ANGT,KG和AT的血清水平比体弱的人低2.05、1.76和2.22倍(所有p <0.05;图1A,2A和3A),并且与握力高度相关(图1B) ,2B和3B)。我们的研究发现,随着年龄的增长,ANGT,KG和AT的水平会增加,因此血管功能的退化可能与虚弱有关。共有226种蛋白质被进行了蛋白质组学分析。体弱的人的血管紧张素原(ANGT),激肽原1(KG)和抗凝血酶III(AT)的水平高于非体弱的受试者(11.26±2.21 vs 5.09±0.74; 18.42±1.36 vs 11.64±1.36; 22.23±1.64 vs 9.52分别为±0.95,p <0.05)。这三个因素与抓地力高度相关(p <0.05),与抓地力和ANGT血清水平(r = -0.89),KG(r = -0.90)和AT(r = -0.84)之间的相关性更高。总之,这是第一项证明老年人体弱的血清蛋白质组学特征的研究。血清ANGT,KG和AT水平可能是监测老年人体弱发育和进展的潜在生物标志物。

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