Green Tea Catechins EGCG and ECG Enhance the Fitness and Lifespan of by Complex I Inhibition

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Oct 5

PMID 34607977

Citations 13

Authors

Jing Tian

Caroline Geiss

Kim Zarse

Corina T Madreiter-Sokolowski

Michael Ristow

Affiliations

Soon will be listed here.

Abstract

Green tea catechins are associated with a delay in aging. We have designed the current study to investigate the impact and to unveil the target of the most abundant green tea catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG). Experiments were performed in to analyze cellular metabolism, ROS homeostasis, stress resistance, physical exercise capacity, health- and lifespan, and the underlying signaling pathways. Besides, we examined the impact of EGCG and ECG in isolated murine mitochondria. A concentration of 2.5 μM EGCG and ECG enhanced health- and lifespan as well as stress resistance in . Catechins hampered mitochondrial respiration in after 6-12 h and the activity of complex I in isolated rodent mitochondria. The impaired mitochondrial respiration was accompanied by a transient drop in ATP production and a temporary increase in ROS levels in . After 24 h, mitochondrial respiration and ATP levels got restored, and ROS levels even dropped below control conditions. The lifespan increases induced by EGCG and ECG were dependent on AAK-2/AMPK and SIR-2.1/SIRT1, as well as on PMK-1/p38 MAPK, SKN-1/NRF2, and DAF-16/FOXO. Long-term effects included significantly diminished fat content and enhanced SOD and CAT activities, required for the positive impact of catechins on lifespan. In summary, complex I inhibition by EGCG and ECG induced a transient drop in cellular ATP levels and a temporary ROS burst, resulting in SKN-1 and DAF-16 activation. Through adaptative responses, catechins reduced fat content, enhanced ROS defense, and improved healthspan in the long term.

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References

Hasumura T, Shimada Y, Kuroyanagi J, Nishimura Y, Meguro S, Takema Y . Green tea extract suppresses adiposity and affects the expression of lipid metabolism genes in diet-induced obese zebrafish. Nutr Metab (Lond). 2012; 9(1):73. PMC: 3489561. DOI: 10.1186/1743-7075-9-73. View

Brenner S . The genetics of Caenorhabditis elegans. Genetics. 1974; 77(1):71-94. PMC: 1213120. DOI: 10.1093/genetics/77.1.71. View

Schroeder E, Kelsey N, Doyle J, Breed E, Bouchard R, Loucks F . Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal. 2008; 11(3):469-80. DOI: 10.1089/ars.2008.2215. View

Byerly L, Scherer S, Russell R . The life cycle of the nematode Caenorhabditis elegans. II. A simplified method for mutant characterization. Dev Biol. 1976; 51(1):34-48. DOI: 10.1016/0012-1606(76)90120-2. View

Tullet J, Hertweck M, An J, Baker J, Yun Hwang J, Liu S . Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 2008; 132(6):1025-38. PMC: 2367249. DOI: 10.1016/j.cell.2008.01.030. View

Back P, Braeckman B, Matthijssens F . ROS in aging Caenorhabditis elegans: damage or signaling?. Oxid Med Cell Longev. 2012; 2012:608478. PMC: 3431105. DOI: 10.1155/2012/608478. View

Murphy C, McCarroll S, Bargmann C, Fraser A, Kamath R, Ahringer J . Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003; 424(6946):277-83. DOI: 10.1038/nature01789. View

Abbas S, Wink M . Epigallocatechin gallate from green tea (Camellia sinensis) increases lifespan and stress resistance in Caenorhabditis elegans. Planta Med. 2008; 75(3):216-21. DOI: 10.1055/s-0028-1088378. View

Yang W, Hekimi S . Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell. 2010; 9(3):433-47. DOI: 10.1111/j.1474-9726.2010.00571.x. View

10.

Schafer F, Buettner G . Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001; 30(11):1191-212. DOI: 10.1016/s0891-5849(01)00480-4. View

11.

Yu R, Chen C, Mo Y, Hebbar V, Owuor E, Tan T . Activation of mitogen-activated protein kinase pathways induces antioxidant response element-mediated gene expression via a Nrf2-dependent mechanism. J Biol Chem. 2000; 275(51):39907-13. DOI: 10.1074/jbc.M004037200. View

12.

Stefanatos R, Sanz A . Mitochondrial complex I: a central regulator of the aging process. Cell Cycle. 2011; 10(10):1528-32. DOI: 10.4161/cc.10.10.15496. View

13.

Bigelow R, Cardelli J . The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene. 2006; 25(13):1922-30. DOI: 10.1038/sj.onc.1209227. View

14.

Grove K, Lambert J . Laboratory, epidemiological, and human intervention studies show that tea (Camellia sinensis) may be useful in the prevention of obesity. J Nutr. 2010; 140(3):446-53. PMC: 2821884. DOI: 10.3945/jn.109.115972. View

15.

Suh K, Chon S, Oh S, Kim S, Kim J, Kim Y . Prooxidative effects of green tea polyphenol (-)-epigallocatechin-3-gallate on the HIT-T15 pancreatic beta cell line. Cell Biol Toxicol. 2009; 26(3):189-99. DOI: 10.1007/s10565-009-9137-7. View

16.

Oh S, Mukhopadhyay A, Dixit B, Raha T, Green M, Tissenbaum H . Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat Genet. 2005; 38(2):251-7. DOI: 10.1038/ng1723. View

17.

Murphy C . The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol. 2006; 41(10):910-21. DOI: 10.1016/j.exger.2006.06.040. View

18.

Dresen A, Finkbeiner S, Dottermusch M, Beume J, Li Y, Walz G . Caenorhabditis elegans OSM-11 signaling regulates SKN-1/Nrf during embryonic development and adult longevity and stress response. Dev Biol. 2015; 400(1):118-31. DOI: 10.1016/j.ydbio.2015.01.021. View

19.

Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, Guthke R . Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol Metab. 2013; 2(2):92-102. PMC: 3817383. DOI: 10.1016/j.molmet.2013.02.002. View

20.

Pullikotil P, Chen H, Muniyappa R, Greenberg C, Yang S, Reiter C . Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF-α. J Nutr Biochem. 2011; 23(9):1134-45. PMC: 3296830. DOI: 10.1016/j.jnutbio.2011.06.007. View