Anti-ageing effects of selected marine microalgae in PC12 cells and drosophila melanogaster

Abstract

Ageing is a progressive impairment of function causing decreased defense against environmental challenges and increased risk of many diseases. The development of ageing and ageing-related diseases might be attenuated by nutrients such as carotenoids and polyunsaturated fatty acids. In the present study, for the first time, two nutrient-rich marine microalgae, namely Haematococcus pluvialis (HP) and Schizochytrium mangrovei (SM) were studied for their anti-ageing effects both in vitro and in vivo.

Results of nutritional profile analysis confirmed that HP is rich in astaxanthin (AX) (978.9 μg/g). Using rat adrenal medulla pheochromocytoma (PC12) cells as an in vitro model, AX exhibited significant protective effects against oxidative stress induced by H2O2 or amyloid β-peptide (Aβ). To testify whether AX conveys such effects to HP, the anti-ageing property of HP was subsequently investigated on Drosophila melanogaster. In the group of SODn108 mutant fruit flies, lifespan elongation effect was observed, where HP may play as a complement of the defective endogenous antioxidant system to extend the lifespan and ameliorate the age-related decline of locomotor function. On the other hand, a long-term intake of HP (20 mg/mL) induced early mortality of wild type fruit flies, which was associated with the decreased enzymatic activities of CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) as well as mRNA down-regulation of SOD1, SOD2, and Catalase (CAT). Further study showed that HP supplementation contributed to the defense of wild type OR fruit flies against chronic but not intensive oxidative stress. The observed ‘bifacial effect’ could be resulted from ‘hormesis’ responses, suggesting the therapeutic instead of the preventive potential of HP against ageing-related diseases.

Another microalga SM was found to contain abundant docosahexaenoic acid (DHA) (53 mg/g). The in vitro studies showed that SM failed to protect PC12 cells under H2O2-induced oxidative stress due to its poor anti-oxidative activity. However, from in vivo studies, the SM supplementation significantly extended the lifespan of both wild type and SODn108 mutant fruit flies and ameliorated the age-related decline of locomotor function. Further studies revealed that the observed activities were associated with the mRNA up-regulation of endogenous stress-defending genes such as SOD1 and SOD2, as well as the down-regulation of methuselah (MTH) gene.

It has been proposed that antioxidants may protect DHA against oxidative damage. To determine whether there is a synergistic effect for HP and SM, a mixture of these two algal samples was evaluated for its effects on the lifespan of D. melanogaster. Results showed that the wild type fruit flies fed with the mixture had no elevated survival rate, tentatively suggesting that the increased nutritional complexity may trigger elevated metabolic rate and lead to shortened lifespan.

In conclusion, results of the present study demonstrated the anti-ageing properties of nutrient-rich microalgae both in vitro and in vivo, suggesting SM possesses the potential to be used as a preventive diet supplementation, while HP may be a suitable candidate as therapeutic agents. Based on these findings, the health benefits of nutrient-rich microalgae for the elderly as well as patients with ageing-related diseases were proposed.