The pursuit of eternal youth and immortality has a long tradition. As far back as 2000 years ago, Alexander the Great was searching for the mystic fountain of youth. Nowadays scientific efforts are more realistic, though no less ambitious. Numerous reports describe genetic manipulations that result in an extension of lifespan in laboratory animals. Surprisingly, this can also be achieved by a controlled but drastic reduction in nutritional uptake. But how realistic are starvation or genetic engineering as life-prolonging techniques in humans? These are certainly not desirable options – but do alternatives exist? In fact, nature offers a suite of molecules – namely the tannins – that may prove to offer attractive alternatives.
Tannins are polyphenols produced by plants. Amongst other purposes, these compounds guard against stress. They are abundant in wine, tea, various berries and nuts. A special feature is their inhibiting action with respect to ingestion and food utilization. Could this characteristic be the key to increased longevity? This question might be answered by one of the most popular model organisms, the roundworm Caenorhabditis elegans. This laboratory animal, about one millimetre in length, has excellent properties for research, including simple cultivation, a short lifespan and a relatively undemanding existence. The worm also has a relatively strong genetic analogy to humans and so has been utilized to study the ageing process, as well as complex diseases like Alzheimer’s, cancer and diabetes. For these reasons, we selected C. elegans as a tool to define how tannins affect lifespan.
Ideal Candidates for an Investigation
In our study, we tested tannic acid, which is often used as a flavouring agent in wine, juices and soft drinks, as well as the most frequently occurring tannin building blocks in nature: gallic acid, ellagic acid and catechin. Tannic acid in particular exhibited impressive properties, increasing the lifespan of C. elegans from an average of 10.5 to 15.4 days – an extension equivalent to almost 50%. Translated directly to humans, this would imply an extension of the current mean lifespan of about 80 years to 118 years. Of course, a worm is not as complex as a human and this calculation is highly speculative and intended for illustrative purposes only.
But what are the precise mechanisms that drive tannic acid-mediated longevity? Tannic acid may decrease food utilisation or at least mimic this effect at a molecular level. To investigate this hypothesis, we selected genetically modified roundworms containing specific gene deletions that result in a chronically decreased ingestion and subsequent longevity. The lifespan of these worms were not extended by tannic acid, offering at least circumstantial evidence that the same “starvation-mechanism” (also called caloric restriction) may be responsible for tannic acid-mediated longevity.
Moreover, tannic acid seems to act in a hormetic fashion – hormesis describes a reversal in response between low and high doses of various stressors and toxins. In other words, tannic acid was life-prolonging at low concentrations, but life-shortening at higher doses. It is conceivable that tannic acid might exert a mild stress at low concentrations, which trains and activates the stress defence of an organism. This is also supported by the fact that tannic acid-treated roundworms were more tolerant to certain stressors, including heat and exposure to oxidants.
A Demonstration of It’s Toxic Potential
But is there another side to the coin? The most effective tannic acid concentration also resulted, in parallel to longevity, in an inhibition of growth and a delayed onset of the reproductive period. This is in line with Thomas Kirkwood’s theory, which states that the additional energy required for life prolongation is removed from other sectors, such as growth. Furthermore, even low concentrations of tannic acid affect the regulation of more than 600 genes, with consequences that are complex and often not directly obvious.
Whilst only a narrow range of concentrations result in longevity, the life-shortening properties at higher concentrations clearly demonstrates the toxic potential of this tannin. Therefore, prior to vindicating the intake of tannic acid – for example as dietary supplements – it is of paramount importance to define via clinical trials the optimum concentration needed to maximize the benefits and suppress possible toxic side effects. Moreover, the scientific community is still searching for direct evidence that tannins mediate longevity in humans. Thus, it may be questioned whether tannic acid will ever be exploited to act as a fountain of youth, a notion that may in fact not be desirable at all!