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

Abstract

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.

Keywords: Angiotensinogen; Antithrombin III; Kininogen-1; Proteomics; Strength.

Figure 1

(A) Serum levels of angiotesinogen (ANG) in frailty and non-frailty. *, p < 0.05. (B) Relationship between the grip power and serum ANG level. Serum ANG level was negatively correlated with grip power (r = -0.89, p < 0.05) in elders with non-frailty. Elders with frailty and non-frailty are represented by the filled triangles and open circles, respectively.

Figure 2

(A) Serum levels of kininogen-1 (KG) in frailty and non-frailty. *, p < 0.05. (B) Relationship between grip power and serum KG level. Serum KG level was negatively correlated with grip power (r = -0.90, p < 0.05) in elders with frailty. Elders with frailty and non-frailty are represented by the filled triangles and open circles, respectively.

Figure 3

(A) Serum levels of antithrombin III (AT) in frailty and non-frailty. *, p < 0.05. (B) Relationship between grip power and serum AT level. Serum AT level was negatively correlated with grip power (r = -0.84, p < 0.05) in elders with frailty. Elders with frailty and non-frailty are represented by the filled triangles and open circles, respectively.