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Aging and disease    2018, Vol. 9 Issue (2) : 220-227     DOI: 10.14336/AD.2017.0423
Orginal Article |
Exploration of Novel Anti-Oxidant Protein Sestrin in Frailty Syndrome in Elderly
Rai Nitish1, Venugopalan G.2, Pradhan Rashmita2, Ambastha Akash2, Upadhyay Ashish Datt3, Dwivedi Sadanand3, Dey Aparajit B.2, Dey Sharmistha1,*
1Department of Biophysics,
2Department of Geriatric Medicine,
3Department of Neurology,
4Department of Biostatistics, All India Institute of Medical Sciences, New Delhi - 110029, India
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Abstract  

Frailty in elderly is very much familiar with a decline in the musculoskeletal system. Muscle degeneration in the lower organism was observed due to loss of anti-oxidant protein Sestrin. The aim of the study is to determine the level of Sestrin1 and Sestrin2 in the serum of frail and non-frail elderly to associate their impact in frailty syndrome. Subjects with age ≥ 65 years were enrolled from Geriatric Medicine OPD of All India Institute of Medical Sciences, New Delhi (N= 92). Among them, 51 subjects were identified as frail and rest 41 were regarded as non-frail according to “deficit accumulation model of Rockwood.” The study was performed by surface plasmon resonance and validated by western blot. Sestrin1 and Sestrin2 were found to be significantly reduced in frail compare to non-frail elderly. Furthermore, even after the adjustment for age, gender and education, the level of Sestrin1 and Sestrin2 remain significantly lower across the groups. The Sestrin1 level was significantly lower in various categories like age, gender, BMI, education, ADL, number of co-morbidity along with other clinico-pathological features. ROC analysis also revealed the distinction of frail and non-frail in respect to serum Sestrin1 and Sestrin2. This study highlighted the new and promising role of serum Sestrin in frail and non-frail elderly. In future, it can be utilized as molecular marker to assess the potential diagnostic value for clinical purpose.

Keywords Serum      Surface Plasmon Resonance      Protein marker      Immunoblot     
Corresponding Authors: Dey Sharmistha   
About author:

These authors contributed equally to this work.

Issue Date: 01 April 2018
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Rai Nitish
Venugopalan G.
Pradhan Rashmita
Ambastha Akash
Upadhyay Ashish Datt
Dwivedi Sadanand
Dey Aparajit B.
Dey Sharmistha
Cite this article:   
Rai Nitish,Venugopalan G.,Pradhan Rashmita, et al. Exploration of Novel Anti-Oxidant Protein Sestrin in Frailty Syndrome in Elderly[J]. Aging and disease, 2018, 9(2): 220-227.
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http://www.aginganddisease.org/EN/10.14336/AD.2017.0423     OR     http://www.aginganddisease.org/EN/Y2018/V9/I2/220
FrailNonfrailp-value
N5141
Age76.55 ± 6.8276.12 ± 5.570.747
Female n (%)30 (58.8)8 (19.5)0.000
Male n (%)21 (41.2)33 (80.5)0.000
BMI (Kg/m2)22.57 ± 5.0923.26 ± 4.210.492
Gait speed (m/s)0.44 ± 0.160.72 ± 0.140.000
Grip strength (Kg)12.19 ± 8.8332.24 ± 13.580.000
OA knee n (%)23 (45.1)10 (24.4)0.04
Joint pain n (%)25 (49.0)13 (31.7)0.094
Fall n (%)17 (33.3)5 (12.2)0.018
Sleep disorder n (%)13 (25.5)2 (4.9)0.008
ADL17.72 ± 3.2019.73 ± 0.590.000
Malnutrition n (%)45 (88.2)12 (29.3)0.000
Table 1  Demographic data of frail and nonfrail subjects: age, BMI, gait speed and grip strength illustrated as mean ± S.D.
Figure 1.  Surface Plasmon Resonance. Immobilization of (A) anti-human Sesn1 IgG and (B) anti-human Sesn2 IgG on the CM5 sensor chip. The linear standard curve, obtained by plotting different response unit (RU) against their respective concentration, showing the binding of increasing concentration of purified (C) Sesn1 and (D) Sesn2 with their respective antibody, resulting in a corresponding increase in RU values.
ProteinUnadjusted/AdjustedFrailNonfrailp-value
Sesn1Unadjusted14.58 ± 0.34 (13.9-15.3)17.61 ± 0.55 (16.5-18.7)0.000
Adjusted14.69 ± 0.43 (13.8-15.5)17.43 ± 0.48 (16.5-18.4)0.000
Sesn2Unadjusted12.74 ± 0.30 (12.1-13.3)14.14 ± 0.41 (13.3-14.9)0.003
Adjusted12.8 ± 0.36 (12.1-13.5)14.06 ± 0.40 (13.2-14.9)0.030
Table 2  Unadjusted and Adjusted (for age, gender and education) serum protein levels (mean ± S.E.) (95% confidence interval) (ng/µl) of frail and nonfrail subjects.
Figure 2.  Serum Sestrin level. Scatter graph showing the levels (ng/µl) of serum (A) Sesn1 and (B) Sesn2 in frail (n=51) and nonfrail (n=41) subjects. The serum concentration, estimated by SPR technology, showed a significant decline of Sesn1 (p<0.0001) and Sesn2 (p = 0.003) in frail compare to nonfrail. ROC analysis showing the area under curve for (C) Sesn1 and (D) Sesn2 to differentiate between frail and nonfrail. The area under curve for Sesn1 = 0.74 and Sesn2 = 0.65. The western blot followed by density analysis was performed to confirm the differential expression of (E) Sesn1 and (F) Sesn2 in the serum of frail and nonfrail subjects. Lane 1-5: frail; Lane 6-10: nonfrail. For E and F, values are expressed as Intensity/mm2 for frail and nonfrail
Sesn1Sesn2

FrailNonfrailp-valueFrailNonfrailp-value
Age
65-7415.50 ± 2.3618.19 ± 3.850.01013.04 ± 2.014.45 ± 2.510.040
75-7914.75 ± 2.8718.21 ± 3.560.00512.78 ± 2.5714.52 ± 3.140.060
≥8013.67 ± 2.0516.46 ± 3.150.00112.47 ± 2.0313.49 ± 2.130.080
Gender
Male14.71 ± 2.1017.71 ± 3.470.00012.96 ± 1.4514.21 ± 2.650.026
Female14.48 ± 2.7517.22 ± 4.050.01512.59 ± 2.5513.86 ± 2.520.110
BMI
≤2314.92 ± 2.4618.23 ± 3.750.00212.31 ± 1.8514.16 ± 2.770.011
>2314.39 ± 2.5116.96 ± 3.270.001112.98 ± 2.2914.13 ± 2.460.040
Education (Years)
014.81 ± 2.6917.59 ± 3.380.01613.02 ± 2.1414.04 ± 2.260.228
1-815.19 ± 1.9916.23 ± 2.490.25712.76 ± 2.1812.81 ± 1.980.953
9- 1212.84 ± 2.9319.30 ± 4.290.02811.06 ± 2.2715.86 ± 3.030.016
≥1313.29 ± 1.6617.76 ± 3.830.00912.61 ± 2.0814.29 ± 2.600.357
ADL
Impaired14.56 ± 2.7317.97 ± 4.020.00312.71 ± 2.3514.45 ± 3.720.048
Normal14.63 ± 1.7517.52 ± 3.480.00312.84 ± 1.5914.07 ± 2.310.038
No. of comorbidity
114.49 ± 2.3617.13 ± 3.360.00112.78 ± 2.0913.81 ± 2.370.042
>114.72 ± 2.7318.44 ± 3.810.00112.69 ± 2.3014.72 ± 2.930.015
Grip strength
Weak14.62 ± 2.5718.11 ± 3.870.00012.75 ± 2.2114.83 ± 2.890.006
Normal14.13 ± 1.1317.38 ± 3.430.05612.67 ± 1.6413.83 ± 3.430.266
Gait speed
Slow14.63 ± 2.5515.73 ± 2.440.44712.71 ± 2.2312.39 ± 1.420.682
Normal14.21 ± 2.0117.93 ± 3.630.00713.03 ± 1.5414.45 ± 2.640.209
Joint pain
Yes14.34 ± 2.6917.21 ± 3.320.00312.53 ± 2.5113.84 ± 2.240.062
No14.81 ± 2.2917.80 ± 3.680.00012.95 ± 1.7514.29 ± 2.770.020
OA knee
Yes15.19 ± 2.6317.59 ± 3.830.02313.34 ± 2.5914.52 ± 3.040.013
No14.07 ± 2.2717.62 ± 3.510.00012.25 ± 1.5914.02 ± 2.470.001
Fall
Yes14.05 ± 2.3518.76 ± 4.580.03112.47 ± 2.1914.74 ± 4.520.170
No14.84 ± 2.5317.45 ± 3.420.00012.89 ± 2.1514.06 ± 2.300.015
Table 3  The concentration of serum Sesn1 and Sesn2 (ng/µl) as mean ± SD with different clinico-pathological features.
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