EVALUATION OF THE GEROPROTECTIVE EFFECT OF SQUALENE ON THE CAENORHABDITIS ELEGANS MODEL

Abstract

Background. Increasing healthy life expectancy is a priority in modern healthcare. Squalene, a triterpene exhibiting antioxidant, anti-inflammatory and other properties, is a promising candidate for geroprotectors.
 Purpose. Assess the activity of squalene, that is, the possibility of its further use as a geroprotector.
 Materials and methods. Squalene was purchased from Sigma-Aldrich (USA) for research. Squalene solutions were prepared with concentrations of 10, 50, 100, 200, 400, 800, and 1600 µmol/L (solvent dimethyl sulfoxide—DMSO). The work was carried out on the basis of the Laboratory for Biotesting of Natural Nutraceuticals (KemGU, Russia). Antioxidant activity was assessed by capturing ABTS radical cations in comparison with the activity of ascorbic acid. The model organism Caenorhabditis elegans N2 Bristol was purchased from the Laboratory for the Development of Innovative Medicines and Agrobiotechnologies of the Moscow Institute of Physics and Technology. To assess the stress resistance of nematodes during cultivation, conditions of thermal (33°C) and oxidative (adding 15 μl of 1 M paraquat, 20°C) stress were created for 24 and 48 h. conditions (20 °C) for 61 days. The statistical significance of the results was assessed using Student’s t-test (in Microsoft Office Excel 2007). Lifespan data were assessed using a Kaplan-Meier survival plot combined with a log-rank test (Mantel-Cox). Data processing was carried out using the OASIS online application (https://sbi.postech.ac.kr/oasis/).
 Results. The results showed that squalene solutions did not exhibit antioxidant properties; did not trap radical cations with ABTS. A solution of squalene at a concentration of 10 μM contributed to an increase in the stress resistance of nematodes. Under conditions of oxidative stress, the survival of nematodes during cultivation for 24 hours is 3.1% higher than in the control. Under conditions of heat stress during cultivation for 48 hours, the survival rate is higher by 11.3%. Squalene solutions did not affect the lifespan of nematodes.
 Conclusion. Presumably, the antioxidant activity of squalene is expressed not in the capture of free radicals, but in the ability to act on biomolecules that lead to oxidative stress. A squalene solution with a concentration of 10 μM can reduce the negative impact of one of the factors causing premature aging. In order to assess the possibility of using squalene as a geroprotector without relying on cation-radical capture, further studies are needed to study the impact of the substance on other targets, mechanisms of action related to the occurrence of age-associated diseases. For example, analysis of the effect of squalene solutions on the growth rate of C. elegans larvae, the ability to influence the expression of antioxidant defense genes, the presence of anti-inflammatory and other properties.