Epigallocatechin-3-gallate promotes healthy lifespan through mitohormesis during early-to-mid adulthood in Caenorhabditis elegans
Li-Gui Xiong,
Yi-Jun Chen,
Jie-Wen Tong,
Yu-Shun Gong,
Jian-An Huang,
Zhong-Hua Liu
Affiliations
Li-Gui Xiong
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China; Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, Hunan, 410128, China
Yi-Jun Chen
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China
Jie-Wen Tong
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China
Yu-Shun Gong
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China; Correspondence to: The 11th North Building, Nongda Road 1#, Furong District, Changsha, Hunan Province, China.
Jian-An Huang
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China; Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, Hunan, 410128, China; Correspondence to: The 11th North Building, Nongda Road 1#, Furong District, Changsha, Hunan Province, China.
Zhong-Hua Liu
Key Laboratory of Tea Science of Ministry of Education, Hunan Agricultural University, Changsha, Hunan, 410128, China; National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, Hunan, 410128, China; Collaborative Innovation Centre of Utilisation of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha, Hunan, 410128, China; Correspondence to: The 11th North Building, Nongda Road 1#, Furong District, Changsha, Hunan Province, China.
The green tea polyphenol epigallocatechin-3-gallate (EGCG) is widely consumed as a dietary supplement. Its potential properties include slowing aging and extending lifespan, although how exactly this is achieved remains unclear. Here, we report that EGCG promoted healthy lifespan in Caenorhabditis elegans when administered throughout or only at early-to-mid adulthood. Specifically, EGCG extended lifespan in an inverted U-shaped dose-response manner. The life-extending mechanism was stimulated by EGCG-induced production of reactive oxygen species (ROS). Additionally, EGCG triggered mitochondrial biogenesis to restore mitochondrial function. The EGCG-induced increase in lifespan depends on known energy sensors such as AMPK/AAK-2, as well as SIRT1/SIR-2.1 and FOXO/DAF-16. Interestingly, aging decreased the response to EGCG and progressively neutralized its beneficial effects on longevity. Collectively, our findings link EGCG to the process of mitohormesis and suggest an inducible, AMPK/SIRT1/FOXO-dependent redox signaling module that could be invoked in different contexts to extend healthy lifespan. Its effectiveness is higher in younger adults and declines with age. Keywords: Epigallocatechin-3-gallate, Healthy lifespan, Mitohormesis, Early-to-mid adulthood, AMPK, C. elegans
