Astaxanthin promotes the longevity of Caenorhabditis elegans via modulation of the intracellular redox status and PHA-4-mediated autophagy.

Abstract

Astaxanthin is a xanthophyll carotenoid which has been associated with a number of health-promoting effects, including anti-aging; however, the underlying mechanisms are not fully understood. In the present study, it was found that astaxanthin promoted the longevity of wild-type (N2) Caenorhabditis elegans (C. elegans). The lifespan-extending effect of astaxanthin was associated with a significant decrease of lipofuscin accumulation and the reduction of the age-related decline in spontaneous motility. Meanwhile, astaxanthin enhanced the oxidative stress resistance in C. elegans, preventing the elevation of the reactive oxygen species and alleviating juglone-induced toxicity. Further studies revealed that astaxanthin treatment induced the expression of the skn-1 gene; besides, the lifespan-extending effect of astaxanthin relied on SKN-1. Additionally, the expression of age-1, a PI3K homolog gene, and let-363, a target of the rapamycin (TOR) homolog gene, was decreased, while the expression of PHA-4, a transcription factor negatively regulated by TOR signaling, was increased by astaxanthin treatment. PHA-4 has been demonstrated to regulate the expression of genes playing critical roles in the autophagy-lysosome pathway (ALP). Consistently, several key genes related to ALP, including lgg-1, atg-5, vps-34, ncr-1 and asm-1 were upregulated in C. elegans treated with astaxanthin. Knockdown of pha-4 expression by siRNA prevented the elevation of the above ALP-related genes, while diminishing the lifespan-extension effect of astaxanthin. Overall, these results indicated that astaxanthin prolonged the lifespan of C. elegans via modulating the intracellular redox status and promoting PHA-4-mediated autophagy.