Kill old age in the bud
Ann Underwood, "Russian Newsweek", 12/15/2008
At 18 days old, the average roundworm is usually already old, weak and sluggish. He is unlikely to live longer than 20 days. Unless Cynthia Kenyon, director of the Hillblom Center for the Biology of Aging at the University of California, San Francisco, worked with him. By modifying two genes, Kenyon was able to extend the worm's life to 144 days. "They can be subjected to tortures that an ordinary worm would never tolerate: exposure to high temperatures, radiation and microbes. They don't die," the researcher boasts. – Moreover, they look young. It looks like a miracle, but it's science."
People have long dreamed that something similar would be done to them. In the last century, hygiene, antibiotics, vaccines and medical care in general have already extended human life by about 50%: in the USA – from 48 years among men and 51 among women in 1900 to 75 and 80 today, and in Russia – from 29 years and 31 years to 59 and 72 years. But now most scientists are trying to prolong not old age, but youth. "I want to give people the opportunity to stay healthy longer and reduce the burden on the economy," says Harvard molecular biochemist David Sinclair.
Some scientists even give specific recipes. However, there is nothing in them that our ancestors would not have known 100 years ago. We are talking about regular physical activity and a diet with lots of fruits, vegetables and cereals. Seventh-day Adventists eat vegetables, do not smoke and spend a lot of time with family and in church groups, protecting themselves from stress. "It's common for them to live somewhere up to the age of 88," says Dr. Thomas Perls, head of the New England Centenarians project.
Of course, to live up to 100 years, as 1,500 participants in the Perls study, a virtuous life alone is not enough. It is necessary to have favorable variants of the genes responsible for the mechanisms of aging. Some similar genes have already been identified, but this is most likely just the tip of the iceberg. Happy owners of the right gene variants almost do not get sick, even ignoring all the rules. "We had a man who smoked three packs a day," Perls says. – He quit smoking at 90, but still drank three glasses of martinis every day and repaired the roof of his house on his own for the rest of his life. He died at the age of 103."
Perhaps the parents gifted this smoker with genes that are involved in metabolic processes and are responsible for the processing of fats and cholesterol. Cynthia Kenyon proved that not only nature can activate such genes. Kenyon managed to regulate a gene in worms that weakens the effects of insulin and the related hormone IGF-1. "Lowering the level of this hormone activates the FoxO gene,– Kenyon explains. "And it stimulates the whole chain of reactions that protect cells and strengthen the immune system, increasing the level of antioxidants, ensuring proper protein folding." In addition, IGF-1 is believed to play an important role in the mechanisms of cancer formation.
However, if longevity depends only on genes, then there is no hope for most of us yet: today only one in 6,000 Americans and one in 15,000 Russians live to be 100 years old. It is assumed that the same result can be achieved in other ways. One of them is a harsh low–calorie diet. Mice that eat 30% less than others live 1.5 times longer. A ten-year study on rhesus monkeys shows that the same effect can be observed in primates.
Dr. Luigi Fontana from the University of Washington Medical School observed 45 members of the Low-Calorie Nutrition Society for 12 years who voluntarily went on such a diet. "The heart of each of them is 15 years younger than the average of people of their age," Fontana is surprised. – And the pressure is like that of teenagers." The level of their C-reactive protein (an indicator of inflammatory processes in the body) was much lower than the maximum allowable.
Tedd Ottman, a 53-year-old programmer from California, has been on this diet since 2002. He consumes only 1,500 calories a day and carefully ensures that the body gets everything it needs. For 6 years, Ottman lost about 20 kg and learned to cope with the side effects of his diet: hunger pangs, decreased libido and a feeling of cold. But his cholesterol level has noticeably dropped and now he gets better sleep.
Of course, Fontana's research does not prove that fasting prolongs life. By the way, not everyone can decide to do this. Many such experiments are generally contraindicated. Dr. Sinclair from Harvard hopes to develop pills that will give the same beneficial effect, but without side effects. Two years ago, he published a study on a red wine-based drug called resveratrol. Obese mice received concentrated doses of the drug and at the same time felt as good as their skinny counterparts. In addition, they lived longer and were hardier. And this year the experiment was repeated on skinny mice. After a course of resveratrol, they suffered less from cataracts and heart disease, their bones were stronger, and their motor skills were better.
Both with the use of resveratrol, and with diet, and with physical exertion, the SIRT1 protein from the sirtuin family is activated. It increases the production of new mitochondria – cellular power plants – and stimulates existing ones. A study published by Sinclair a month ago shows that SIRT1 also repairs chromosome breaks. This helps to keep the "rejuvenating" genes in working order and turn off the "aging" ones. Kenyon confirms that SIRT1 improves the same metabolic process that it affected in its worms.
Another candidate for the elixirs of youth is a drug that restores telomeres, the tips of DNA on the edges of chromosomes. During cell division, telomeres are shortened. When they become too short, the cells stop multiplying, work worse and eventually die. This is aging. Scientists hope to prevent these effects by increasing the production of telomerase, an enzyme that compensates for the shortening of telomeres. "Occasionally there are people with very low levels of telomerase," says molecular biologist Elizabeth Blackburn from the University of California, San Francisco. "As a rule, they do not live to old age, dying from infections, cancer and lung fibrosis."
Experiments show that mice with elevated telomerase levels live 40% longer. In addition, they have stronger skin and stronger immunity. To what extent these results are applicable to a person is an open question. Rita Efros from the University of California at Los Angeles last month published the results of immunological experiments conducted with HIV patients. Their cells were affected with the help of a telomerase activator. "These cells killed the virus better, retained the ability to divide longer and behaved like younger ones," Efros says. On the other hand, when there is too much telomerase in the body, the risk of cancer formation increases. "To make sure that telomerase drugs are safe, long and time–consuming studies are needed," Blackburn believes.
But some are impatient. Telomere specialist Bill Andrews from Sierra Sciences takes TA-65, a supplement that stimulates the production of telomerase. "I'm sure it's safer than driving from home to work," he laughs. According to Andrews, having started taking TA-65 a year and a half ago, he has greatly improved his results in ultramarathon races for 100 miles. TA-65 is not found in pharmacies. The drug is sold only by TA Sciences, and the annual course costs $25,000.
Kenyon and Sinclair also put the development of "rejuvenating" drugs on industrial rails. Both Sirtris Pharmaceuticals, which Sinclair founded, and Elixir Pharmaceuticals Kenyon are developing pills for diabetes, one of the main age–related diseases. Initial tests have confirmed that resveratrol reduces the level of sugar and insulin in the blood of patients suffering from type 2 diabetes. Then the company began testing a synthetic sirtuin activator, a thousand times stronger than resveratrol. "Six major pharmaceutical companies are working on the production of sirtuin," says Dr. Christoph Westphal, head of Sirtris. "Because it affects many diseases associated with aging, its potential market is huge." In the summer, pharmaceutical giant GlaxoSmithKline bought Sirtris for $720 million.
Portal "Eternal youth" www.vechnayamolodost.ru23.01.2009