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Seeking the fountain of youth

Researchers have figured out how to extend the lives of yeast, worms, flies and rodents by 30-40 per cent. This increase in longevity has been mainly due to a protected environment, improved healthcare and vigilant lifestyles. To achieve a further 50 per cent increase in human longevity, scientists are faced with twin options: Should they try to delay the ageing process itself, or should they bolster the body

Researchers have figured out how to extend the lives of yeast, worms, flies and rodents by 30-40 per cent.

This increase in longevity has been mainly due to a protected environment, improved healthcare and vigilant lifestyles. To achieve a further 50 per cent increase in human longevity, scientists are faced with twin options: Should they try to delay the ageing process itself, or should they bolster the body’s ability to ward off the diseases of ageing? What is more, any approach to longevity should ensure that aged people continue to lead a healthy and productive life even at the age of 110 or 120 years.

Considering the complexity of the ageing process, scientists are experimenting with different routes of slowing down this process. Through genetic engineering, at least 15 longevity genes have been manipulated to extend the life of organisms. Cells have a built-in programme that prevents them from replicating (or reproducing) more than a predetermined number of times. These cells, called senescent cells, play a leading role in making us look and feel old&emdash;causing wrinkles, failing eyesight and chronic inflammation. Genetic modification seeks to prevent the accumulation of these senescent cells either through overcoming this natural programming so that they divide indefinitely, or by ensuring that some senescent cells die.

Another approach to anti-ageing focuses on cellular wear and tear caused by free radicals, as the main cause of ageing. Normally, free radicals are produced within the cell when oxygen is used to burn food into energy. Free radicals are toxic and attack all molecules&emdash;DNA, proteins and lipids&emdash;within the cell. Over time, the attacks wear down the cells, leaving them vulnerable to disease, just as rust weakens a car’s structure. Unfortunately, formation of free radicals is a natural process. As we age, more and more free radicals are produced, causing greater damage. One major anti-ageing approach would thus be to prevent damage caused by free radicals by turning up activity of enzymes naturally produced by the body to break the free radicals down. A number of experiments based on this concept have extended the lifespan of fruit flies and worms by a third.

The most publicised approach&emdash;the effort to extend life through extreme calorie restriction&emdash;has been proved to slow down ageing in several species. Calorific restriction simply means a diet with fewer calories that still delivers the required nutritional content. Cutting daily calorie intake by 30 per cent in mice extended their lifespan by 30 per cent to 40 per cent.

Path-breaking work by Dr Leonard Guarente at the MIT has shown that the SIR2 gene in yeast silences genes that cause ageing in an organism. When food is plentiful, the SIR2 protein is in a passive mode. But when food supplies are low due to calorie restriction, the SIR2 gene silences the ageing genes, thereby increasing the yeast’s life. Research is now focusing on the SIRT1 gene&emdash;the equivalent gene in humans. This gene could also explain the health benefits often attributed to red wine: Resveratrol&emdash;a substance in the skin of grapes&emdash;has been found to activate SIRT1. Other substances in blueberries, red wine and spinach also possess similar properties that extend life.

It however seems unlikely that old people would like to prolong life by nearly starving themselves. Consequently, scientists are searching for ‘‘calorie-restriction mimetics’’&emdash;that is, drugs that would trick the body into thinking it is on a drastically reduced diet. Such drugs are likely to be developed in the next 5-10 years. If successful, people would start enjoying a maximum life span of 170 years, most of it in perfect health.

Research has also identified the inability to deal with stress as an important ageing factor. Stress increases production of chemicals called catecholamines, which increase the risk of blood pressure, diabetes and heart disease. Evidence also suggests a role for hormones. Deft manipulation of estrogen, progesterone, testosterone, thyroid, growth hormone and melatonin&emdash;all of which decline with age&emdash;may preserve certain aspects of youthful vigour.

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