Hormesis Of Epigallocatechin-3-gallate (EGCG) To Antiaging

Epigallocatechin-3-gallate (EGCG), which is the major and most abundant catechins in green tea, has been demonstrated to possess a wide range of physiological and pharmacological activities, including antioxidant, anti-inflammatory, anti-radiation and reducing serum lipids. Studies on the effects of green tea or EGCG on the lifespan of normal individuals have been quite limited and rather controversial or non-conclusive. Based on the previous researches, the primary objective of this study is to investigate effects of EGCG on Caenorhabditis elegans, a model organism, and the underlining machanisms. The main results are summarized as followings:(1) The lifespan analysis after treatment with increasing concentrations of EGCG during the full adult lifespan of wide-type C. elegans N2 suggested that EGCG concentration is positive with the lifespan of C.elegans from 0 to 300 μM, no obvious effects from 300 to 500 μM and negative from 500 to 1000 μM.EGCG modulated N2 lifespan, cultured on differents E.coli OP50 (Live, arrested and pretreated with EGCG), is independent on its antibacterial property. EGCG modulated N2 lifespan, cultured with or without CAT, is independent on H2O2 formed by EGCG autooxidation in NGM.(2) To further evaluate how lifespan modulated by EGCG, experiments were performing by limiting the duration (6 days) of EGCG exposure for the early and mid adult life only, initiating EGCG exposure for the different stage adults (day 6,12 and 18 old adults), and measuring the age-related changes with EGCG exposure in C.elegans. These results demonstrated that EGCG modulated C.elegans lifespan span at early-to-mid adulthood.The lifespan assays of wild-type N2 were performing on the NGM without peptone, and the results indicated that the effects of EGCG were less than ad libitum. The lifespan assays of DA465 (eat-2) mutants were performing on the normal NGM, and the results showed that 200 and 1000 μM EGCG modulated the lifespan of DA465 less than wild-type N2.(3) To detect any longevity-extending effects of EGCG under environmental stress, assays were performed under different enviromental stress. The results demonstrated that different concentrations of EGCG exerted different effects under different environmental stresses. In addition, EGCG modulated survival of C.elegans under heat shock in accordance with lifespan under normal conditions. Furthermore, limiting the duration of 200 μM EGCG for the first 6 days protected C.elegans from the shortened lifespan by 1000 μM EGCG.(4) EGCG exposure did not influence reproduction, fertility and larval development.400 and 1000 μM EGCG significantly shortened the body length of C.elegans. EGCG intervention during the larval stage of C.elegans did not influence the adult lifespan of F1, F2 and F6 (from F1 to F5).(5) EGCG (200 and 1000 μM) decreased the ATP and TG contents in C.elegans, induced a transient ROS signal and activated the antioxidant system to clear ROS. Antioxidants (NAC and BHA) prevented EGCG-mediated lifespan regulation.200 μM EGCG increased NAD+ level, and 1000 pM EGCG decreased NAD+ level in C.elegans. Moreover,200 μM EGCG extended C.elegans lifespan dependent on AAK-2, SIR2.1, PRDX-2, PMK-1, DAF-16, SKN-1 and mitochondrial electron transport chain, and independent on HIF-1, SOD-3 and Insulin/IGF-1 signalling pathway. In addition,1000 μM EGCG shortened C.elegans lifespan dependent on SIR2.1. Based on the results of mtDNA/nDNA,200 μM EGCG promoted the mitochondrial biogenesis in C.elegans. Lastly, EGCG did not induce the mitochondrial unfold protein response resulting from the experiments of hsp-6::GFP and hsp-60::GFP reporter worms.