Date Published: April 1, 2018
Publisher: JKL International LLC
Author(s): Nitish Rai, G. Venugopalan, Rashmita Pradhan, Akash Ambastha, Ashish Datt Upadhyay, Sadanand Dwivedi, Aparajit B. Dey, Sharmistha Dey.
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.
Metabolic dysfunction and muscle disorder occur frequently in the elderly. Therefore, the maintenance of muscle strength and healthy mobility in the elderly is necessary for optimal functioning. The onset of frailty brings changes in various organs that contribute to the differential expression and function of an array of proteins. Physical exercise positively regulates PRX system, which is a major scavenger for intacellular hydrogen peroxide thereby exerting a protective effect against oxidative stress-induced damage . Physical exercise has shown to upregulate the PRX isoforms in skeletal and heart muscle cells . Inactivated or mutated Sesn in preclinical studies of C. elegans and Drosophila shows muscle degeneration [18, 22]. Physical exercise can upregulate Sesn, which inhibits mTOR and prevents age related frailty symptoms . Sesn are regulated by p53, with serum p53 increased after vigorous exercise . Gene silencing of Sesn1 and Sesn2 results in ROS accumulation, highlighting the importance of Sesn1 and Sesn2 in endogenous antioxidant regulation . The exercise-related benefits could be attributed to the antioxidant and AMPK-modulating functions of Sesn.