Key Points:
- EGCG consumed over an 18-month period confers a 46.96% average lowered risk of death and a ~25% median lifespan increase in mice.
- EGCG suppresses the age-related buildup of the p21 senescence-associated protein in fat tissue of these mice.
- EGCG counteracts the age-associated decline in autophagy — a cellular process that degrades dysfunctional cellular components as well as recycles proteins — in aged mice.
Senescent cells — dysfunctional cells that emit inflammatory molecules — accumulate as we grow older, and their elimination may serve as a way to revitalize tissues and increase the number of disease-free years we live. As such, it is paramount to identify compounds that mitigate the age-related elevations in senescent cells. This has the potential to enhance our tissues’ functions and reduce systemic inflammation. Along those lines, green tea-derived EGCG has been shown to have senescent cell-eliminating (senolytic) and anti-cancer properties, as well as having the potential to extend lifespan in rats. However, research has not established a correlation between EGCG’s lifespan-extending effects and its senolytic properties until now.
Published in the Journal of Nutritional Biochemistry, Padwad and colleagues from the CSIR-Institute of Himalayan Bioresource Technology in India have shown that EGCG effectively lowers the average risk of death by 46.96% in mice and extends median lifespan by ~25%. The researchers show that EGCG supplementation over an 18-month period counteracts the accumulation of the senescence-associated protein p21 in fat tissue, suggesting EGCG confers a longer median lifespan by mitigating senescent cell buildup in this tissue. Moreover, EGCG supplemented over the same period increases the levels of an autophagy-associated protein, LC3-II, in fat tissue and the intestines. These findings link EGCG consumption’s lifespan extension effects with fat tissue senescent cell reductions and improved autophagy in fat and intestinal tissues.
EGCG Extends Lifespan, Reduces Fat Tissue Senescence, and Improves Autophagy During Aging
To pin down whether EGCG extends lifespan, Padwad and colleagues administered the green tea-derived molecule to mice over the course of 18 months and monitored their naturally-occurring deaths. Intriguingly, the researchers found that EGCG reduced the average risk of mortality across the lifespan by 46.96%. Furthermore, EGCG increased the median lifespan by about 25% in these mice. These data suggest that EGCG supplementation significantly lowers the risk of death and increases median lifespan.
Since age-related senescent cell accumulation has been associated with declining tissue function leading to disease, Padwad and colleagues sought to find whether EGCG reduces a senescent cell protein marker in fat (adipose tissue). The researchers found that the p21 protein marker of senescence showed a statistical trend toward increasing over 18 months in non-treated mice, while EGCG supplementation significantly reduced p21 levels over this period. These results suggest that EGCG counteracts the age-related elevations of p21 protein in fat tissue and thus likely mitigates senescent cell accumulation.
Since an age-related decline in autophagy has been found in rodents and since maintenance of autophagy has been proposed to extend longevity, Padwad and colleagues measured whether EGCG improves the activation of this cellular process. The researchers measured levels of an autophagy-associated protein, LC3-II, in fat and intestinal tissues. Interestingly, LC3-II levels showed a statistical trend toward declining with age in fat tissue. LC3-II also displayed a significant age-related reduction in the intestines of non-treated mice. Along those lines, LC3-II protein levels significantly increased in both tissues with EGCG, suggesting EGCG impedes age-related declines in autophagy. These findings suggest that EGCG preserves autophagy during aging to possibly rejuvenate aged tissues.
“Our results strongly suggest that alleviation of age-dependent [senescent cell] burden and their pathophysiological effects could be one of the key mechanisms of pro-longevity and anti-inflammatory attributes of EGCG,” say Padwad and colleagues.
EGCG May Counteract Two Hallmarks of Aging: Senescence and Compromised Autophagy
Padwad and colleagues show that EGCG supplementation over an 18-month period substantially extends mouse median lifespan and drastically cuts the average risk of mortality. Reducing the abundance of fat tissue senescent cells, as shown with reduced senescence-associated p21 protein levels, was associated with extended lifespan in this study. Along those lines, cellular senescence has been proposed as one of the key hallmarks of aging contributing to age-related declining tissue function, so reducing senescent cells may contribute to lifespan extension. However, since this study only showed a correlation between reduced fat tissue senescent cells and extended lifespan, further research is required to show a causal relationship between these two parameters.
Moreover, EGCG improves the abundance of a protein marker for autophagy — LC3-II. Compromised autophagy has also been proposed as one of the crucial hallmarks of aging. As such, showing that EGCG increases the autophagy-associated LC3-II protein suggests that EGCG counteracts this hallmark of aging as well. By potentially increasing autophagy during aging, EGCG may rejuvenate cells and tissues to possibly improve health during aging.
A major limitation to the study was that EGCG’s effects on senescence and autophagy were only examined in a few tissues — fat and intestinal tissues. Future studies should examine whether EGCG alleviates senescence and improves autophagy in other tissues like the brain, kidneys, and skin.
If someone wants to purchase EGCG for supplementation, a month’s supply is available online for between $10 and $35 per bottle. Alternatively, regularly drinking green tea, which contains EGCG, may serve as a way to consume adequate amounts of this molecule for senolytic, pro-autophagy, and potential healthspan-promoting effects. For a dosage equivalence based on the EGCG given to mice in this study, one would need to consume approximately eight cups of green tea daily.
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