·    C. elegans treated with EGCG and ECG reached an average lifespan extension of 6.9% and 6.2%, respectively.
·    Life span extension by EGCG and ECG involves the activation of energy sensors, ultimately boosting oxidative stress resistance.
·    The long-term effects also included reduced fat content in C. elegans after five days of catechin treatment.

Tea is one of the most widely consumed beverages worldwide. First consumed as a drink or medicine by the Chinese population around 4500 years ago, tea stimulates the central nervous system and cardiac function in humans and has been linked to delayed aging for many years. Clinical trials have revealed health benefits of green tea consumption: a significant reduction in systolic blood pressure and weight loss in type 2 diabetes patients and women with obesity.

New research from the Institute of Nutrition at the Friedrich Schiller University in Germany shows that low doses of green tea catechins EGCG and ECG extend the lifespan of the roundworm C. elegans, a commonly studied animal in aging. The effects of EGCG and ECG on lifespan extension appear to be mediated by the ability of the catechins to improve the function of the cell’s power generators (mitochondria) and reduce the amounts of harmful compounds called reactive oxygen species (ROS), which are the targets of antioxidants. This study, published in Aging, adds to the growing list of experiments showing that green tea catechins have beneficial effects on animal lifespan, which, in the past decade, has been demonstrated in flies and male mice.

What is green tea, and what is it made of?

On average across the world population, a person consumes half a cup of tea per day. Tea is available in three primary forms — green, oolong, and black tea — depending on the antioxidants’ level and the degree of fermentation. Tea mainly consists of polyphenols, caffeine, minerals, and trace amounts of vitamins, amino acids, and carbohydrates.

The caffeine in tea leaves ranges between 2% and 5%, depending on the age of the leaf, wherein younger leaves will have a higher concentration. The type of polyphenols present in tea will vary depending upon the level of fermentation it has undergone. 

Green tea mainly consists of compounds called catechins, whereas black tea mainly contains tannins. Notably, green tea is considered the most predominant source of catechins among all dietary sources, ahead of chocolate, red grapes, wine, and apples. Compared to other forms of tea, green tea is richer in antioxidants, and the most abundant form in green tea leaves is catechins, which form up to around 40% of solid green tea extract. 

What do we know about green tea’s beneficial effects?

Experiments in various model organisms suggested a beneficial effect of green tea catechins on lifespan due to metabolic adaptation and enhanced resistance to reactive oxygen species (ROS). For instance, dietary supplementation with EGCG-rich green tea extracts (10 mg/mL EGCG) affected glucose metabolism and increased flies’ health and lifespan. Besides, green tea polyphenol-containing water (80 mg/L) extended the lifespan of male C57BL/6 mice. 

However, the poor bioavailability of green tea catechins in mammals makes it unlikely to achieve this concentration after oral administration in humans. Nevertheless, several independent clinical trials confirmed that green tea consumption improves various health parameters. After administration of a maximum of 4.5 grams of decaffeinated green tea solids, maximum plasma concentrations of EGCG, ECG, and EC reached roughly 2.5 μM in humans.

EGCG and ECG enhance the fitness and lifespan of C. elegans 

For these reasons, Tian and colleagues tested whether 2.5 μM is still sufficient to promote lifespan by inducing a pro-survival response called mitohormesis in C. elegans. This work reveals that EGCG and ECG enhance fitness and increase the lifespan of C. elegans already at a concentration of 2.5 μM. Indeed, EGCG and ECG applied at a concentration of 2.5 μM were sufficient to significantly extend the medium lifespan of C. elegans from 28.8 days to 30.8 and 30.6 days, respectively. The maximum lifespan increased from 35.7 days to 36.9 and 37.1 days by EGCG and ECG treatment, respectively. That equates to reaching a life extension of 3.4% for EGCG and 3.9% for ECG.

(Tian et al., 2021 | Aging) Increased lifespan after EGCG and ECG treatment. The representative outcome of lifespan assay of nematodes in the presence of 2.5 μM EGCG (left) or ECG (right) versus the control (DMSO).

Next, Tian and colleagues tested whether prolonged lifespan also correlates with improved fitness and stress resistance. Locomotion is dependent on functional muscle mass, connective tissues, and neuronal signaling. Consequently, motility is a suitable marker for health. EGCG and ECG treatment improved the nematodes’ motility after seven days of incubation. Moreover, treating C. elegans with ECGC and ECG for seven days significantly increased stress resistance to the ROS generator paraquat. Consequently, EGCG and ECG enhanced fitness and stress resistance, both crucial parameters for health.

(Tian et al., 2021 | Aging) Increased stress resistance after EGCG and ECG treatment. The representative outcome of the survival analysis (h) of N2 nematodes in 50 mM paraquat solution after seven days of pretreatment with EGCG (D) or ECG (E) in comparison to worms pretreated with DMSO. P-values are as indicated in the graphs.

EGCG and ECG improve ROS balance and cellular metabolism

Tian and colleagues then looked at the effects of EGCG and ECG on the function of mitochondria and ROS. The researchers found that, at first, after 6 to 12 hours of exposure to 2.5 μM, EGCG or ECG reduced mitochondrial function in C. elegans. However, mitochondrial function recovered and even improved after 24 h and 120 h of treatment with EGCG and ECG. The time course of initial diminution and the subsequent recovery of mitochondrial function correlates with ROS levels, which increased significantly after 6 hours of ECGC and 12 hours of ECG administration and dropped significantly after 24 and 120 hours of catechin treatment. In line with this, the fat content was considerably lower after 120 hours of EGCG or ECG treatment, pointing to a catechin-induced long-term reprogramming of cellular metabolism.

(Tian et al., 2021 | Aging) EGCG and ECG induce adaptive responses to ROS. Reactive oxygen species (ROS) production in C. elegans after treatment for 6, 24, or 120 hours with 2.5 μM EGCG (left) or ECG (right) compared to control (DMSO).

EGCG treatments increased the activity of major antioxidant enzymes in C. elegans called superoxide dismutases (SODs) and catalases, which turn stress-inducing hydrogen peroxide back into neutral water. Tian and colleagues found that EGCG led to increases in SOD activity after 24 hours and catalase activity after seven days. Meanwhile, ECG treatments did not significantly increase SOD activity but increased catalase activity after 24 hours and seven days. The enhanced activity of SOD and catalase correlates with the subsequent drop of ROS levels after 24 hours of EGCG and ECG treatment. Notably, when Tian and colleagues blocked the SODs and catalases, the lifespan-extending effect of EGCG and ECG were lost, indicating that the effect of EGCG and ECG on lifespan is dependent on SODs and catalases.

Will EGCG extend lifespan in humans?

These data validate a link between mitochondria, antioxidants, and lifespan control, which should warrant further research into EGCG or green tea (plant polyphenols) and ways of applying these compounds to improve healthy aging or for other therapeutic indications. “We show that already 2.5 μM of EGCG and ECG, a concentration also potentially achieved after green tea consumption, are sufficient to induce an extension of lifespan and increase stress resistance by adaptational mechanisms,” conclude Tian and colleagues.

As it pertains to humans, we know that daily supplementation with EGCG is safe, as one clinical study showed that one year of 400 mg EGCG consumed daily was safe. This study further revealed that plasma concentrations of EGCG reached a measurable level after six months. What’s more, several independent clinical trials have confirmed that green tea consumption improves various health parameters. Although it is currently difficult to test the effects of any compound on lifespan extension in humans, it seems that the positive impact of green tea on health has stood the test of time and is being reinforced by work in research labs around the world.

(Tian et al., 2021 | Aging) The green tea catechins EGCG and ECG at a low dose extend the lifespan of C. elegans via inducing a mitohormetic response. In this model, the inhibition of mitochondrial 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. 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.