Green tea catechins extend the lifespan of C. elegans

Aging-US published "Green tea catechins EGCG and ECG enhance the fitness and lifespan of Caenorhabditis elegans by complex I inhibition" which reported that green tea catechins are associated with a delay in aging. The authors have designed the current study to investigate the impact and to unveil the target of the most abundant green tea catechins, epigallocatechin gallate and epicatechin gallate.

Catechins hampered mitochondrial respiration in C. Long-term effects included significantly diminished fat content and enhanced SOD and CAT activities, required for the positive impact of catechins on lifespan. Through adaptative responses, catechins reduced fat content, enhanced ROS defense, and improved healthspan in the long term.

Dr. Corina T. Madreiter-Sokolowski and Dr. Michael Ristow said, "Clinical trials and epidemiological studies have revealed health benefits associated with green tea consumption, including a significant reduction in systolic blood pressure and fasting glucose as well as weight loss in type 2 diabetes patients and in women with central obesity"

The most abundant polyphenols in green tea leaves are epigallocatechin gallate, epicatechin gallate, epigallocatechin, and epicatechin, forming 30–42% of the solid green tea extract. EGCG accounts for roughly 50% and ECG for 20% of the total catechin amount in green tea leaves. A randomized, placebo-controlled clinical trial testing a daily supplementation with 400 mg EGCG confirmed the safety of a one-year administration with EGCG.

Besides, green tea polyphenol-containing water extended the lifespan of male C57BL/6 mice.

Moreover, treatment of Caenorhabditis elegans with EGCG at concentrations of 50–300 μM during early-to-mid adulthood promoted lifespan, and 200 μM EGCG was the most potent dosage to extend lifespan via inducing a mitohormetic response via AMPK/SIRT1 and FOXO.

However, the poor bioavailability of green tea catechins in mammals makes it unlikely to achieve this concentration after oral administration in humans. Experiments in isolated murine liver mitochondria revealed that EGCG and ECG hamper complex I activity. Inhibition of complex I was accompanied by transient ROS formation and an ATP drop after 6 h of EGCG and 12 h of ECG treatment in C. elegans.

Lifespan extension of C. elegans by EGCG and ECG proved to be dependent on the presence of the energy sensors AMP-activated kinase AAK-2 and NAD-dependent protein deacetylase SIR-2.1, the homologs of mammalian AMPK and SIRT1, as well as on the ROS-sensing mitogen-activated protein kinase PMK-1, the orthologue of mammalian mitogen-activated protein kinase p38 MAPK, and in the following on its downstream targets protein skinhead-1, the orthologue of nuclear factor erythroid 2-related factor 2, and DAF-16, the orthologue of a mammalian forkhead transcription factor.

The Madreiter-Sokolowski/Ristow Research Team concluded in their Aging-US Research Output, "applying the green tea catechins EGCG and ECG at a low dose extends the lifespan of C. elegans via inducing a mitohormetic response. Thereby, the inhibition of complex I causes a transient ROS rise that stimulates the antioxidant defense enzymes SOD and CAT and activates the PMK-1/SKN-1/DAF-16 pathway (Figure 6, Scheme). Besides, complex I inhibition causes a temporary drop in cellular ATP levels and consequently activation of AAK-2/SIR-2.1 signaling. In the long term, the re-wiring of these energy- and ROS-dependent pathways reduces the fat content and extends health- and lifespan."