In search of the secrets of longevity

The quest for the test tube of youth
Carolyn Abraham, Globe and Mail, 09.01.2009
Translation: GerovitalAs children, they won at tag, then won the war and defeated the patriarchy.

Now the baby boomer generation wants to outsmart Grandfather Time. The fear of death and senile infirmity drives science to research how to preserve health and strength until old age. But isn't trying to cheat senility and death a futile dream?

Noel Thomas Patton was 50 when he made the decision that he would not give up just like that. He was born in December 1945, on the eve of the baby boom, and considers it a matter of honor not to follow in the footsteps of previous generations - just "sit in a rocking chair, play checkers, watch TV, and then die."

Today he is 63 and he wants to keep his wits sharp, play tennis, ski and dance for at least another decade. "I really like discos," he says.

In his opinion, a long and full life is possible if all parts of the body work well. Some parts are already known to him, mostly mechanical – blowers, motors, belts and knives. The American entrepreneur made his fortune on electric fans and heating appliances. But after selling his business in 1995, and in the same year he began to feel ailments "here and there," he applied his ingenuity to parts of the body – in particular to human cells.

Mr. Patton believes he has found a way to keep the cell functioning for a long time. For the past 18 months, he has been taking an extract of astragalus, an ancient Chinese herb that is said to protect cells from wear and tear over time. In addition, he sells his medicine – a one–year course of treatment costs $ 25,000 - and claims that there are doctors and even scientists among his clients.

There is no direct evidence of the drug's effectiveness yet, but if they appear, it will become a real sensation: we will learn how to prolong the existence of a healthy cell and possibly increase the duration of a full life.

History knows a lot of hunters for the elixir of youth. The legionaries searched for him in the waters of Babylon, in the beds of young virgins and in the legendary power of monkey testicles. Walt Disney and baseball star Ted Williams were hoping to find him on ice. Ponce de Leon (Ponce de Léon) was sure that he would find him gushing from the Florida soil. And now Mr. Patton, a multimillionaire, eager to realize his hopes with the help of science, has joined the age-old search for a way to prolong youth.

And he chose the time as well as possible. Having pulled the idea out of the arms of charlatans and scammers, scientists began to work. Reputable researchers in pursuit of a regenerative drug are studying stem cells, looking for the secrets of longevity in the genes of fruit flies, flatworms and centenarians. Dozens of serious companies are developing anti-aging products. Bruce Ames, one of the most cited scientists, winner of the Medal for Scientific Achievements of the USA, founded a company called Juvenon.

However, so far no one has managed to stop the running of the biological clock. But just as the baby boom increased the production of diapers, vests, strollers and miniskirts, as the number of those who evaded military service increased and stock options increased, so their march against death gives research in the field of aging a global priority.

Partly, and because scientists themselves are getting old. But governments are also concerned about the burden of caring for an aging population. It is expected that by 2050 the number of people over the age of 80 will increase fourfold and amount to about 400 million people. The surge in research has become "something of an apocalyptic response to demographic realities," says Anne Martin-Matthews, research director of the Institute on Aging, one of the divisions of the Canadian Institute of Medical Research (Institute of Aging, part of the Canadian Institutes of Health Research). "We want to identify those factors that will contribute to improving the health of the population, so that we do not exhaust all the resources available today."

Scientific studies of the aging process have become so famous that the language has become replenished with quite specific words – "geroscience" (the science of aging), "welldly" (healthy elderly people), "health span" (the years of life that a person lived while healthy).

In Europe, an extensive five-year study is aimed at studying the genes of almost 2,700 brothers and sisters over 90 years of age from 11 countries. A Well Elderly study is being conducted in the USA, during which scientists plan to learn more about the relationship between physical activity and a healthy aging population.

Next year, 160 Canadian researchers from several universities will launch the Canadian Longitudinal Study on Aging, which will involve 50,000 men and women from 45 to 85 years old. The study is expected to last at least 2 decades; attention will be paid to biological, psychological, social and economic changes. According to experts, it will be the largest study of the aging process ever conducted.

The Canadian Institutes of Health Research (CIHR – Canadian Institutes of Health Research)– the main financier of medical research in Canada, spent $136 million last year on research in the field of aging – an amount 5 times higher than the costs of 2000-2001. Currently, the Institute on Aging receives about 14% of the total CIHR budget, up from 6% nine years ago.

Progress is progressing so rapidly that many researchers today consider aging as a series of degenerative diseases, the appearance of which can be postponed or even prevented. Such a prospect has even caused a number of serious discussions about the limits of human life; one can hear bold predictions that the average North American girl born today will live 100 years.

"Today we have all the necessary tools – we understand the genetics of the process, its metabolism, and all this is now much easier to assess and manage," says Dr. Ames from California. "I think that we will be able to push back all age-related degenerative diseases and, thereby, extend the life of each person for several years."

Financing

In Canada, it all started in 2001, when the CIHR called on scientists to conduct research on the aging process. Angela Brooks-Wilson, a senior researcher at the Cancer Agency of British Columbia in Vancouver, was studying genetic susceptibility to cancer, but soon realized that in order to obtain additional financial resources, it was possible to change the direction of research somewhat.

"This is another proof of how institutions that provide funding can contribute to research in a particular field of science," explains Ms. Brooks–Wilson, and jokingly adds, "After all, the employees of these institutions are also aging."

She expanded her research and decided to study the genes of elderly people who had not suffered any serious diseases. Dr. Brooks-Wilson argues that "human life expectancy largely depends on ecology and lifestyle, but 30% is genetics." By the end of 2002, the CIHR had provided her with $1.25 million to conduct a five-year study of people of "very advanced age".

These 550 people from Vancouver and its environs were selected based on data from the British Columbia Ministry of Health. The age of people ranges from 85 to 105 years, besides, they have never had such age-related diseases as cancer, lung problems, Alzheimer's disease, diabetes or cardiovascular diseases.

Two-thirds of them are women (who, as a rule, live longer than men). Barbara Roberts, for example, lives alone in the eastern part of the city, and in her 90s continues to clean the snow in front of the house herself. "She is an amazing, energetic woman," says Dr. Brooks-Wilson. "A real zippy."

Observing the "super-strong", scientists study 25 different genes involved in metabolism and tumor suppression. They match their DNA with the DNA of 550 randomly selected men and women aged 40 to 50 years - two-thirds of whom, according to statistics, will not live to 85. The researchers want to find out whether the centenarians have any common genetic traits that the representatives of the control group do not have.

The results of the study are expected at the beginning of this year. Meanwhile, a group of British Columbia scientists have discovered something interesting about the telomeres of the "super elderly".

Telomeres are one of the hottest molecules in medicine. Like plastic caps on the ends of a shoelace, telomeres are, in fact, tails at the ends of chromosomes that protect genetic information from "wear".

But telomeres are also biological time bombs: they shorten every time a cell divides, and the longer we live, the more the cell divides.

Telomeres, which are actually a repeating specific DNA sequence (TTAGGG), eventually wear out and turn into unstable nodules. At this point, the cell begins to collapse and die, and our bones become thinner, the chin begins to sag and cancer begins.

It makes no sense to talk about a huge interest in finding a way to stop the telomere clock.

As it turned out, the telomeres of "super-long-livers" do not differ in particular length, but their sizes are more or less the same, while the representatives of the middle-aged control group had significant differences.

The theory is that if the telomere is too long, then the cell divides more than it should, increasing the risk of cancer. But if the telomere is too short, then the cell may suffer from premature genetic damage, which is also fraught with disease.

In a paper published last November, Dr. Brooks-Wilson and telomere expert Peter Lansdorp suggested that the telomere length in centenarians is optimal, which explains "disease resistance and healthy old age."

Immortal cells

Mr. Patton had never heard of telomeres until 1999, when he was invited to a gala dinner dedicated to fundraising for aging research in Palm Desert, California (Palm Desert, Calif.).

By this time, he had spent about four years looking for a doctor who would "help him really get younger." However, according to him, he came across mostly some merchants. Then he attended a lecture on telomeres by Jerry Shay, a renowned specialist in cell biology from the University of Texas Southwestern Medical Center.

Dr. Shai, whose research formed the basis of the telomeric theory of aging, described how activating an enzyme called telomerase "could prolong the existence of telomeres and make cells immortal."

In a healthy cell, telomerase is usually disabled. But the gene that produces it is usually included in stem and cancer cells, each of which, having the ability to multiply indefinitely, is "theoretically immortal."

Mr. Patton immediately turned to Dr. Shy, who told him that the University of Texas had transferred the license for telomeres to the Geron Corporation of California, an influential biotech firm that in 1997, in collaboration with the university, discovered the telomerase gene and funded the first human stem cell research.

The next morning, Mr. Patton called the CEO of Geron and made a major investment in the company. He learned that the corporation was hunting for a compound that would activate the production of telomerase, and that to this end it was negotiating with researchers from the University of Science and Technology in Hong Kong (University of Science and Technology in Hong Kong) to study some such compounds from China.

By pure chance, Mr. Patton, along with his wife Eva and two children, also lives in Hong Kong, where he moved in 1987, deciding to establish the production of fans and heaters in mainland China. From there, he assisted in the negotiation process, and scientists were able to test 50 compounds of traditional Chinese medicine.

One of these compounds was astragalus, a pointed shrub from the Inner Mongolia Autonomous Region. For thousands of years, the Chinese have used this plant to strengthen immunity, normalize blood pressure and improve the general condition of a person. It is added to soups or sauces and brewed instead of tea. The extract of this plant can be found in any specialty diet food store.

According to Patton, testing of astragalus showed that this plant really stimulates the activity of telomerase in human cell cultures.

Geron, who was then engaged in cancer and stem cells, did not set herself the task of developing a drug based on astragalus.

But Patton wasn't going to wait.

In 2002, he created his own company, TA Sciences, in Manhattan (where he now lives from time to time). He agreed with Geron on a license to use astragalus extract as a non-medicinal product. Positioning his product as a dietary supplement and without making any statements about its medicinal properties, he develops his alternative drug, being independent of the regularly reviewed regulations of the FDA (US Food and Drug Administration).

Clogged cells

Bruce Ames has never been involved in research on the aging process, let alone the formation of a company selling anti-aging products. The 80-year-old biochemist, who worked at the University of California at Berkeley and the Children's Hospital Oakland Research Institute, devoted most of his career to the study of DNA damage. In the 1960s, he developed the Ames test, still the gold standard for detecting carcinogens.

But as he discovered the causes of cancer, he caught himself thinking about aging. "It is obvious that cancer is a disease of the elderly," he says. "By the age of 80, about 1/3 of the entire population gets sick with it."

The researcher notes that we bring a significant part of the damage to ourselves. Seventh-day Adventists who do not smoke, drink or eat meat have cancer twice as rare and they live on average two years longer. (When asked what ultimately kills them, he jokes, "Boredom.")

Ames' scientific work is aimed at combating some of the causes of aging, namely, such an alarming phenomenon as mitochondrial extinction.

Mitochondria are the engines of the cell, transforming the oxygen, fats and sugar we consume into energy. But just as engines emit exhaust gases, the cellular process of energy conversion pollutes cells in its own way - free radicals are produced, highly active atoms and molecules that accumulate in cells over time.

There comes a time when smog from free radicals destroys DNA, as well as the functionality of the cell. Paradoxically, the processes by which we live – breathing and nutrition – eventually kill us.

In 2002, in the prestigious Proceedings of the National Academy of Sciences, Dr. Ames reported that he and his colleague Tory Hagen may have found a way to slow mitochondrial extinction. They came to the conclusion that two compounds that can easily be found in any diet store – lipoic acid and acetyl-L-carnitine (in Italy it is sometimes also used as a tonic) – improve the functioning of mitochondria, as well as physical and mental activity of aging rats.

As Dr. Ames likes to say: "These old rats took and danced macarena."

A friend of Ames persuaded him to found a company called Juvenon and sell a complex of two compounds. Ames agreed to become the scientific director of Juvenon on the condition that all profits – and the monthly rate of the drug costs about $ 30 – will be directed to clinical trials.

Currently, Dr. Ames is making a self-funded crusade (he has mortgaged his house) in order to convince scientists and governments that a very common deficiency of trace elements is at the root of many age-related degenerative diseases. He claims, for example, that in cells that lack magnesium, telomeres shrink much faster.

Guinea pig

Patton still had to wait: "It took five years and millions of dollars until I had a pill in my hands that was completely safe for health."

Since mid–2007, he has been taking 50 mg of astragalus extract daily - twice as much as he prescribes to his clients, but still only 1/1000 of the amount toxic to human cells.

He admits that he feels "like a guinea pig." But at the same time adds: "I feel great, I have increased energy, libido, my immune system has strengthened. People around me say that my skin looks better, healthier."

He used to be bothered by the joint of his right knee, especially when playing tennis, but now the pain has disappeared. Did the extract of astragalus help in this? "I can't say for sure," Patton admits. But he claims: laboratory studies at the University of California confirmed that the drug rejuvenated his immune system.

Increased telomerase activity leads to the formation of cancer cells, but, according to Patton, taking his pills can cause cancer only theoretically. He refers to studies that suggest that oncological diseases are the result of a number of mutations, and not just telomerase activation. It is also reassuring that the Chinese have been drinking tea from astragalus for centuries in the same way as we eat chicken soup.

Mr. Patton, however, based on the tests of four well-known brands of astragalus extract, claims that the extract of astragalus sold in pharmacies does not contain the active element that is part of his drug. Of the 2,000 compounds that make up the plant, TA Sciences isolated a molecule that it named TA65. "To get a small amount of this substance, we needed three tons of the plant."

Mr. Patton cannot say whether his pill is similar to the compound from astragalus, which Geron is currently engaged in – the company plans to develop a drug to activate telomerase in cells of the immune system. But he claims that it is no less effective.

The Geron version (its drug is called TAT2) was the subject of an article in the November issue of the peer-reviewed Journal of Immunology. According to scientists, this compound enhances the ability of the immune system to fight HIV.

The lead author of the study, Rita Effros, professor of pathology and laboratory medicine at the University of California, Los Angeles, collaborated with Geron in 1996 and testifies that in people with HIV, killer T cells have shortened telomeres.

Killer T cells can be compared to soldiers standing on the front line of the immune system. With age, they gradually lose their functionality, partly due to the constant fight against viruses. That's why older people are particularly vulnerable to flu and other infections.

The T-cells of people infected with HIV are constantly waging war against the AIDS virus, so there are relatively few functionally healthy T-cells left.

"The immune system of such people looks like in diseases of premature aging," says Dr. Efros.

And he adds: "We know that in people who are not able to get AIDS, telomerase activity in killer T cells is higher."

In earlier experiments, Dr. Efros demonstrated that injecting the telomerase gene into a T cell taken from infected patients prevented telomeres from shortening and allowed cells to fight HIV more successfully. But this is in the laboratory, and it is impossible to treat people in this way.

As an alternative, Efros and her colleagues tested the astragalus compound: "With TAT2, we got the same telomerase activity as with gene therapy."

"The difference," she says, "is that TAT2 gives us more opportunities – with its help we can control the activity of telomerase: reduce or completely reduce it to nothing."

Dr. Efros believes that this discovery is not limited to HIV treatment. So T-cells, for example, are involved in bone loss. Our bones are constantly being destroyed and restored again. "So every 10 years our skeleton is completely renewed."

But chronic infection, constant activity of T-cells and the immune system disrupt the process of skeletal tissue repair and bones become thinner.

"If it goes on like this, TAT2 will be used for HIV, bone loss and other aging-related diseases," says Dr. Efros. "It's all a distant, rosy prospect."

However, she warns against the idea that the drug can prolong everyone's life. "Anyone who seeks to prolong a person's life is still at the edge of the forest. I am more interested in extending the years of a healthy life – so that you can just drop dead, and not get sick and suffer for 10-20 years before that."

Old, older – the oldest?

Still, some demographers believe that we have many reasons to increase life expectancy in the coming decades.

For centuries, humans, like most species, have died shortly after the end of the reproductive period. Before 1800, the average life expectancy of Europeans was 40 years, and only in 1900 it reached 50. In the following decades, people have achieved stunning success.

In an article published in May 2002 in Science, demographers James Vaupel from Duke University and Jim Oeppen from Cambridge University noted that, since 1840, life expectancy in developed countries has increased by three months every year.

"In 1840, the record for life expectancy belonged to Swedish women who lived on average just over 45 years," the scientists wrote. "Today, Japanese women have the highest life expectancy, almost 85 years."

In industrialized countries, women currently live on average about 80 years, men – a little less. We owe the increase in life expectancy to the improvement of sanitary and hygienic conditions, nutrition, the invention of vaccines and antibiotics, and the latest achievements in the field of medicine.

Taking into account future breakthroughs in the field of genetics and stem cells, many experts believe that the trend of increasing life expectancy will not slow down. But not everyone agrees with this. Jay Olshansky, a leading demographer at the University of Chicago, Illinois (University of Illinois in Chicago), being a supporter of scientific efforts to prolong a healthy period of human life, in an article published in the New England Journal of Medicine in 2005, argues that the increase in the number of obese people can put an end to in the increase in life expectancy observed over the past two hundred years.

Dr. Martin Matthews of the Canadian Institute of Aging claims that there is irrefutable evidence that the limit of human life expectancy is 120 years. But, she adds, everyone will agree that it is pointless to add 40 years to life if "we do not reduce the number of degenerative diseases."

According to Martin Matthews, "it is necessary to balance the rigidity of reliable scientific research with the needs of a graying and impatient market. When scientists from three British Columbia Universities wanted to give a public lecture on how to keep the brain healthy as we age, 1,500 people gathered. I had to look for a large audience."

Despite the fact that such public interest helps to support their research, cautious scientists note that none of the studies of the aging process has yet achieved a breakthrough in this area. In 2002, at the dawn of optimistic life expectancy forecasts, 52 scientists involved in aging research published their views on human aging.

They drew attention to the need to distinguish "the pseudoscientific production of anti-aging products from the genuine science of aging" and stated that there is no way to stop, slow down or reverse the passage of time.

But the hopes of mortals have not decreased.

Salvation or shamanic medicine?In the absence of indisputable evidence, almost 100 people agreed to spend $25,000 annually on the treatment of Mr. Patton's astragalus extract, which he called Patton Protocol.



It all starts with 14 blood vials, which are taken from the client and sent to 4 laboratories for 90 different tests, including for measuring the length of telomeres. (One of these laboratories is the Immunology Laboratory in Los Angeles) The client's cognitive functions, bone density, skin elasticity and vision are also checked.

After six months of taking the extract, the client returns to the company and some biomarkers are re-checked.

"Of course, we are seeing improvements in customers... None of our clients got worse," Mr. Patton comments and adds: "Taking the drug for one year, people continue taking it for the second… No one is going to hire lawyers and sue me."

According to the entrepreneur, he does not advertise his product, because he does not have research results confirming his statements. Most of the clients took his word for it, and "almost all of them are familiar with the biology of telomeres."

"Scientists, doctors of medical sciences buy the extract, and they get not just a pig in a poke. All we offer is a telomerase activator."

Among Mr. Patton's clients, you can find his competitor, Bill Andrews, a researcher who is involved in the discovery of the telomerase gene. Dr. Andrews is now the CEO of Sierra Sciences, a Nevada–based biotech firm. Her motto is: "We will cure aging or die searching." Sierra Sciences itself is trying to develop a telomerase activator.

"If you talk to two telomere biologists, one of them will tell you: "It's too early. It's just a cure in theory. The risk is too great." The other will react like this: "I'm taking this drug. My wife takes it too. Maybe it will save us."

And yet, does Mr. Patton really not care that he sells such an expensive drug without proof of its effectiveness? Here's what he says about this: "If we met somewhere at a party and when you asked me what I was doing, I replied that I was selling a substance that makes cells immortal, then you would think that I said: "I have discovered the elixir of youth for cells." In this case, you would compare me to a charlatan selling nonsense, and I would not be offended."

And more. Previous generations may have accepted aging as an inevitability – "pain, torment, suffering, this is how it should be," he says. But now more and more often you can hear "No, it's not normal, it shouldn't be like this." So baby boomers who feel that they have very little time left to stop the biological clock are ready to accept something that has not necessarily "come out" of the crucible of scientific research.

"Modern society, and first of all baby boomers, lacks patience - we want to continue going to discos, making love and conducting active mental activity," Mr. Patton notes. "And all this is urgent and right now."

However, the lack of results of "20-year double-blind clinical trials" eats it up. He hopes to publish the first peer-reviewed observations about the capabilities of his tablet this year. But in order for the data to be complete and more reliable, more customers are needed. Thus, in the conditions of the global crisis, he had to reduce the price of his drug and now it is just under $ 16,000.

In the end, Patton notes: "It will take at least 30 years to invent a cure for aging. And if you're 80 now, then nothing will help you anymore."

Portal "Eternal youth" www.vechnayamolodost.ru03.03.2009