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Sci Tech
Resveratrol — the molecule that helps fight ageing
— Photo: K.K. Mustafah
Anti-ageing property:The peanut’s pinkish skin contains resveratrol
The groundnuts or peanuts that you buy in snack shops in Gujarat are shelled, roasted and slightly salted. They are also pinkish, since the skin surrounding the nut is intact. This is not true of the salted nuts you buy in the South, or for that matter in many other parts of India. A pity, because there is a nutritional aspect to this pinkish peanut skin.
It contains a molecule called resveratrol, which has some remarkable health-beneficial properties. So next time you peel a peanut shell, do not remove the skin but eat it; it might help you defy ageing in a small but significant manner.
Red wine beneficial
If you should fancy a glass of wine, go for the red wine, since it too contains the magic molecule resveratrol. Researchers have been reporting that drinking a couple of glasses of red wine a day is beneficial; the resveratrol in it helps bring down hypertension, fight diabetes and help retard several ageing-associated metabolic steps.
For several years, scientists have puzzled about the so-called Mediterranean paradox. People in Southern France, Italy, Greece and other Mediterranean regions have been known to be healthier, live longer, not obese and with healthier hearts.
Apart from their life style, it turns out that they eat more fish than meat, white meat than red, greens and mushrooms, eat smaller portions (not filling the tummy, leaving it a little empty), and drink some red wine with every meal. Would any, many or all of these hide the secret to their healthier lives? It appears possible to say that indeed each one of them makes its contribution.
Chemical compounds
Some recent news items have focused on one of these, namely resveratrol in the wine. The first is that the company called Sirtis, which has been aiming to develop chemical compounds with the same effects as resveratrol, has just been bought over by the Pharma giant GlaxoSmithKline (or GSK) for US$720 million.
The owner of Sirtis, Dr. David Sinclair, has said: “the company that dominates the sirtuin space could dominate the pharmaceutical industry and change medicine.”
The reason for this is that resveratrol has properties that activate certain proteins in the body called sirtuins, which play an important role in the body’s ageing process.
Set of proteins
Sirtuins are a set of proteins that affect cellular metabolism by turning on (or off) specific gene expressions. They act on the proteins covering the DNA in our chromosomes.
The long DNA thread or tape in our genome is rolled up in 23 different bundles called chromosomes. These, in turn, and packaged in compact form called the chromatin. And sirtuins are enzymes that act as molecular chisels or sculptors that chip off specific regions from the histone proteins covering the chromatin.
This remodelling of chromatin controls access to the genes or DNA within.
It is this chromatin remodelling that defines how and when the DNA is repaired (when damaged by chemicals, radiation, heat or other stresses), how the message in the DNA is read and translated. In essence, sirtuins are components of the master switch that controls genome stability, prevent alterations and therefore retard some aspects of the ageing process in the long term.
The action of sirtuins themselves is controlled by molecules which stick to them, keeping the activity in abeyance until when needed. And resveratrol removes this restraint, and activates several of these sirtuins.
This exciting finding has been published by a group led by Dr. Richard Weindruch of the University of Wisconsin, in the journal PLosOne (3, e2264, June 2008).
He had earlier shown how eating less (politely called as caloric restriction or CR) retards many aspects of the ageing process — mortality, physiological decline, cancer and so forth. This earlier work has since been validated by others and explains to some extent the Mediterranean paradox.
Experimental animals
The group used mice as experimental animals. To one group, they gave the ‘control’ diet of 84 kilocal per week per animal, to the CR group they gave only 63, and to the third group they gave the control diet plus resveratrol as supplement.
Comparing the latter two groups will give an idea of whether resveratrol mimics the effects of CR in terms of anti-ageing.
The results are interesting. First, looking at heart function, both CR and resveratrol supplementation reduced the age-dependent degradation of some of the cardiac functions.
Next, they found that dietary resveratrol mimics CR in the uptake of glucose in muscles. When they studied the molecular aspects of these by looking at which genes are activated and which de-activated by CR and by resveratrol, the finger pointed to the sirtuin genes. In effect, it appears that both CR and resveratrol may retard some aspects of ageing through alterations in chromatin structure.
Optimal dose
Gluttons should not immediately rush to the store and buy resveratrol, and supplement it to their belly-full lunches and dinners. The Wisconsin experiment is on mice and not men.
What is the optimal dose of the drug for humans is yet to be established, and that would depend on individual physiology and age.
Plus, how much can resveratrol undo the ‘burn-up’ caused by overeating is an issue. Recall that the Mediterraneans do both — CR and red wine; thus they get double benefit; they do not do red wine plus a full stomach.
Being a simple molecule, easily made and purified, it is certain that resveratrol tablets and formulations will flood the market as the anti-ageing miracle drug. Let us add a caveat.
It is not easily soluble in water, and thus can accumulate in fatty tissues — not distribute itself well. Overdosing it might not be that good. Recall the case of people taking too much of vitamin A (carotenes), hoping for greater benefits; it accumulates in fatty tissues and does damage rather than help.
It is this point that has led Dr Sinclair and others to make molecules similar to resveratrol, which should be equally good or better, and soluble.
Better formulations
There are already two organizations in Hyderabad which are working on the issue. One of them studies molecules that would activate the sirtuin proteins, while the other is trying to develop better formulations of resvetratrol itself. I shall look eagerly at their results and eventual products, but until then I shall eat less and drink red wine more.
D. BALASUBRAMANIAM
dbala@lvpei.org
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