Astaxanthin promotes the longevity of <i>Caenorhabditis elegans via</i> modulation of the intracellular redox status and PHA-4-mediated autophagy

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) <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). 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 <i>C. elegans</i>, preventing the elevation of the reactive oxygen species and alleviating juglone-induced toxicity. Further studies revealed that astaxanthin treatment induced the expression of the <i>skn-1</i> gene; besides, the lifespan-extending effect of astaxanthin relied on SKN-1. Additionally, the expression of <i>age-1</i>, a PI3K homolog gene, and <i>let-363</i>, 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 <i>lgg-1</i>, <i>atg-5</i>, <i>vps-34</i>, <i>ncr-1</i> and <i>asm-1</i> were upregulated in <i>C. elegans</i> treated with astaxanthin. Knockdown of <i>pha-4</i> 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 <i>C. elegans via</i> modulating the intracellular redox status and promoting PHA-4-mediated autophagy.