Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegans

Haiyan Chen; Rongji Li; Feng Zhao; Li Luan; Tiantian Han; Zhong Li

doi:10.3389/fnut.2022.960239

Betulinic acid increases lifespan and stress resistance via insulin/IGF-1 signaling pathway in Caenorhabditis elegans

Front Nutr. 2022 Jul 29:9:960239. doi: 10.3389/fnut.2022.960239. eCollection 2022.

Authors

Haiyan Chen^{1

2}, Rongji Li³, Feng Zhao³, Li Luan³, Tiantian Han², Zhong Li²

Affiliations

¹ College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China.
² College of Life Sciences, Changchun Sci-Tech University, Changchun, China.
³ College of Food Science and Engineering, Jilin Agriculture University, Changchun, China.

Abstract

Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 μg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.

Keywords: C. elegans; DAF-16; betulinic acid; lifespan; stress resistance.