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

Exp Gerontol. 2017 Sep:95:9-15. doi: 10.1016/j.exger.2017.05.013. Epub 2017 May 16.

Abstract

Background: 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.

Objectives: 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).

Methodology: 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.

Results: In this cross sectional observational study, the serum concentration of FOXO3A and SIRT3 declined significantly (p<0.0001) with increasing age and even after adjustment with all geriatric co-morbidities the level remain downregulated with age. In the stress inducible cell line showed reduced level of proteins which gets upregulated by the treatment of Ashwagandha.

Conclusion: This is the first report of inverse relation of age with human serum FOXO3A and SIRT3 and can be excellent marker for ageing with good therapeutic importance for maintaining healthy ageing.

Keywords: Ageing; ELISA; FOXO3A; Protein marker; SIRT3; SPR.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Cross-Sectional Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Forkhead Box Protein O3 / blood*
  • Forkhead Box Protein O3 / genetics
  • HEK293 Cells
  • Healthy Aging* / genetics
  • Humans
  • Longevity* / genetics
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Sirtuin 3 / blood*
  • Sirtuin 3 / genetics
  • Surface Plasmon Resonance
  • Withania* / chemistry
  • Young Adult

Substances

  • Antioxidants
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Plant Extracts
  • SIRT3 protein, human
  • Sirtuin 3