Longevity and healthy ageing genes FOXO3A and SIRT3: Serum protein marker and new road map to burst oxidative stress by Withania somnifera

• Published in: Experimental gerontology 2017-09, Vol.95, p.9-15
• Main Authors: Pradhan, Rashmita, Kumar, Rahul, Shekhar, Shashank, Rai, Nitish, Ambashtha, Akash, Banerjee, Joyita, Pathak, Mona, Dwivedi, S.N., Dey, Sharmistha, Dey, Aparajit B.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Ageing; Antioxidants - isolation & purification; Antioxidants - pharmacology; Blotting, Western; Cross-Sectional Studies; ELISA; Enzyme-Linked Immunosorbent Assay; Female; Forkhead Box Protein O3 - blood; Forkhead Box Protein O3 - genetics; FOXO3A; Healthy Aging - genetics; HEK293 Cells; Humans; Longevity - genetics; Male; Middle Aged; Oxidative Stress - drug effects; Phytotherapy; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plants, Medicinal; Protein marker; SIRT3; Sirtuin 3 - blood; Sirtuin 3 - genetics; SPR; Surface Plasmon Resonance; Withania - chemistry; Young Adult
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2017.05.013

Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst. In this study we quantified FOXO3A and SIRT3 proteins in human serum with increasing age and in-vitro assessment of modulation of their expression by the treatment of Withania somnifera (Ashwagandha). Four hundred seventy three subjects were enrolled for the study and were divided into three groups according to increasing age [20–30years (young), 60–79years (old) and ≥80years (oldest)]. Serum levels of FOXO3A and SIRT3 proteins were estimated by Surface Plasmon Resonance (SPR) and validated by ELISA and Western blot. The statistical analysis was done with student's unpaired t-test, one way ANOVA by Stata9 and Graph pad prism5. The expression of these proteins were also analysed in stress induced HEK-293 cell line and level was observed by treatment with stress releasing compound Ashwagandha. In this cross sectional observational study, the serum concentration of FOXO3A and SIRT3 declined significantly (p