Acacetin promotes healthy aging by altering stress response in Caenorhabditis elegans

Abstract

The progression in lifespan has been associated with elevated intracellular reactive oxygen species (ROS) and oxidative stress level which contributes to development of age related disorders. The discovery of lifespan modulating phytomolecules may promote development of natural therapies against age related afflictions. Acacetin (5,7-dihydroxy-4-methoxyflavone), is a naturally occurring flavonoid known to possess therapeutic properties. To this end, the present study evaluates effect of acacetin (AC) on lifespan, stress and neurotoxicity for the first time by using well-established free living, multicellular Caenorhabditis elegans model system. The 25 μM dose of AC significantly prolonged the mean lifespan of worms by 27.31% in comparison to untreated control and other tested doses of AC. Additionally, AC enhanced stress resistance against oxidative and thermal stress in worms. Furthermore, AC attenuated age related intracellular ROS level, aggregation of age pigment lipofuscin and increased the mean survival in stress hypersensitive mev-1 mutant by 40.5%. AC supplementation also reduced the alpha synuclein aggregation in transgenic worm model of Parkinson’s disease. The enhanced stress resistance, lifespan and alleviation of age related pathology can be attributed to increment in stress modulatory enzymes like superoxide dismutase (SOD) and catalase (CAT) level. Altogether the results suggest AC exposure maintains stress level, health span and extends mean lifespan of C. elegans. The longevity promoting and neuromodulatory effects of AC are mediated by up regulation of the stress response genes sod-3 and gst-4. The present finding gives new insights of natural remedies and their future prospects in developing therapeutic interventions for managing age related diseases.

Keywords:

• Acacetin
• Caenorhabditis elegans
• lifespan
• neurodegeneration
• Parkinson’s disease

Acknowledgements

The authors are highly grateful to the CGC, Minneapolis, MN, USA, which is funded by the NIH, National Centre for Research Resources (USA), for providing the C. elegans strains. We thank Miss Aakanksha Pant for editing the manuscript. The authors are thankful to the Director, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India for providing necessary facilities and the help extended by the Head of Department of Biotechnology, IET campus, AKTU, Lucknow, India for his valuable support.

Disclosure statement

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.