Effects Of Astaxanthin On The Lifespan Of C.elegans And The Underlying Molecular Mechanisms

Longevity is the sum of lifespan from birth,growth,maturity,aging to death,and is affected by the genetic and environmental factors which regulate aging rates.Astaxanthin,a natural antioxidant,can effectively reduce the levels of reactive oxygen species(ROS)in both cell and animal models.It has potential preventive effects on a variety of diseases such as cancer,diabetes,gastrointestinal disease,hepatic disease,neurodegenerative diseases and skin diseases.In this study,N2 C.elegans were used as the model to study the effects and the underlying molecular mechanisms of astaxanthin on longevity.The results showed that with 0.5 ?g/m L-20 ?g/m L astaxanthin treatments,the lifespans of worms were prolonged.When the concentrations of astaxanthin were 10?g/m L and 20 ?g/m L,the average lifespans were increased by 14.29% and 19.84%,respectively.The treatments of astaxanthin did not change the body volume and the reproductive ability of the worms,but the treatments of 1 ?g/m L-20 ?g/m L astaxanthin significantly enhanced the locomotivity and the bending frequency of the worms.ROS levels in C.elegans were determined and it was found that the astaxanthin treatments effectively reduced the ROS levels in the worms,causing a 51.22% reduction when astaxanthin was 20 ?g/m L.The stress resistance experiments showed that the astaxanthin treatments(5 ?g/m L-20 ?g/m L)effectively reduced the the elevation of ROS levels induced by oxidative stress and increased the survival rates of the worms.The real-time fluorescence quantitative PCR results showed that the expression levels of sod-1,sod-2,sod-3,ctl-1,ctl-2,ctl-3 and skn-1 had decreasing trends with the treatments of 10 ?g/m L and 20 ?g/m L astaxanthin.And the expression levels of ctl-3were decreased by 25.95% and 38.07% with the treatment of 10 ?g/m L and 20 ?g/m L astaxanthin,respectively.The expression of key genes of the insulin/insulin-like growth factor-1 signaling pathway daf-2,akt-1,akt-2 and daf-16 showed no significant difference compared with the control in C.elegans treated with astaxantin.In contrast,the expression of age-1 gene showed a significant decline and was decreased by 26.35%with the treatment of 20 ?g/m L astaxanthin.The expression of key genes of m TOR signaling pathway,ifg-1 and rsks-1,was not changed significantly with the treatments of10 ?g/m L and 20 ?g/m L astaxanthin,while the expressions of let-363 gene,another key gene of m TOR signaling pathway,was decreased by 55.98% and 58.72% with the treatment of 10 ?g/m L and 20 ?g/m L astaxanthin,respectively.Besides,the expression level of pha-4 gene was increased by 45.99% when the worms were treated with 20?g/m L astaxanthin.It has been shown that knockout or down regulation of age-1 and let-363 genes significantly extends the lifespan of C.elegans,while overexpression of pha-4 gene increases the stress resistence and prolongs the lifespan of the worms.Therefore,astaxanthin might extend the lifespan of C.elegans via affecting on the expression of these genes.In conclusion,the result suggested that astaxanthin effectively extended the lifespan of N2 wide type C.elegans and the underlying molecular mechanisms may be related to the reduction of ROS levels,and the regulation of gene expression in insulin/insulin-like growth factor-1 and m TOR signaling pathways by astaxanthin.This study furthered our understanding of the anti-aging mechanisms of astaxanthin and provided experimental evidence for the future anti-aging application of astaxanthin.