Scientists are working on drugs that will mimic the results of new discoveries in anti aging and life extension research, drugs that will offer all the benefits and none of the self sacrifice made by various species of lab animals. Restricting calorie intake proved successful in extending life when studies were conducted on mice and monkeys. They lived longer and contracted less age related disease but how many of us humans would give up thirty percent of our food intake to maybe add a few more years to our life? What we humans need is a drug that tricks our bodies into believing we are on such a diet.
These would be great drugs for humankind if they ever come to fruition and they may or may not become available. One thing is certain; the drugs are under development and currently in clinical study. Given the track record of drug development, they may not make it out of the lab; so many of them do not. Even if this current research fails, the research bodes extremely well for future investigation into life extension drugs. Researchers will have fresh hope that aging can be manipulated and the potential is there for real progress into combating the complications of advancing age.
For some however, this optimistic view is not something they share. Evolutionary biologists who study aging theories are sharply opposed to the theory that life expectancy of humans can be modified using such rapid and rudimentary methods. All the same, they have been seriously caught off guard by the conclusions of laboratory testing on lab animals such as round worms, fruit flies and mice. Each of these species has exhibited marked enhancements to life spans due to single gene manipulation.
Now that these naysayers of the scientific community have n been silenced, for the time being anyway, research biologists are able to move with confidence with their investigation into what links evolution and food intake, fertility and life expectancy. Many of these “tip of the spear” research scientists simply ignore the evolutionary biologists since according to one acclaimed scientist – “they are always telling others what they cannot think.”
In the anti aging and longevity community, research scientists specifically are quite excited by the results over the last few years. This is due to the clear union between two pathways of investigation: single gene altering and the caloric restriction diet.
With caloric restriction, mice were fed a diet that is nutritious but has thirty percent fewer calories than one would normally eat. These rodents lived thirty to forty percent longer than normal with the only drawback being they become less fertile.
Human beings find it just about impossible to sustain a diet like this, so the formula for longevity stayed a systematic oddity for quite a few years. Then along came the single gene modifications, most of these concern the body’ control mechanisms for development, energy metabolic and reproduction. The single gene changes therefore appear to be targeting those matching biochemical routes that caloric restriction is taking to achieve life extension.
If research scientists could simply recognize these paths, it could be probable that drug development might stimulate them. If these drugs were available, they could have a far greater effect. Rodents on a caloric restriction diet display some defenses against deteriorating diseases of aging, which might well be the reason they live longer lives. Developing a drug that could safeguard humans from some or even all of these degenerative age associated diseases would grant people more years of health, that alone being a great achievement, even if there were no life extension attached to the discovery.
The number one dynamic compound with a prominent part in the research for these drugs is known as sirtuin activators, which appear to be imitating the activity of caloric restriction. Of these compounds, the primary one is resveratrol, a minority element found in grape skins and red wine. Sirtris Pharmaceuticals of Cambridge, Mass., is currently running clinical studies on a unique resveratrol formula and tiny molecular drugs, which can be administered in smaller, doses and activate sirtuin. This formulation of resveratrol and a variety of the small chemicals have made their way through safety testing and currently are being evaluated for their effectiveness to diabetes and other illnesses. The Food and Drug Administration [FDA] will not approve any drug that thwarts aging since aging is not considered to be a disease by the regulatory body.
Sirtuin activators come to the table with a solid scientific resume. The first appeared in research being done in 1991 by Dr. Leonard P. Guarente of M.I.T. that was trying to locate genes that could extend life expectancy in the single cell organism, yeast. Working with Dr. David Sinclair, now of Harvard Medical School, he found the gene, known as sir-2. It was soon discovered that mice and humans also had comparable genes called sirt genes, which generated proteins known as sirtuins.
Dr Guarente soon discovered that these sirtuins can recognize the energy pockets within the cells and are triggered when the energy pockets begin to run low. This is exactly what would be required for a protein that mediates the effect of caloric restriction. Dr. Sinclair and his group evaluated numerous chemical compounds to judge their capability to trigger the sirtuin and resveratrol as it turns out, was the best candidate. Resveratrol was at this time already under suspicion as the reason for the French paradox, meaning the French can consume a diet high in fat and not pay for it in life expectancy.
Both researchers and their teams debated that caloric restriction happens due to the triggering of sirtuins therefore drugs, which stimulate sirtuins, could well provide equal benefits to health.
In 2004, Dr David Sinclair began the company Sirtris Pharma with Christoph Westphal, an entrepreneur scientist. Assisted by increasing attention to the story of sirtuin, Westphal managed to unload the company a year ago to GlaxoSmithKline for a sum of seven hundred twenty million dollars.
According to Sinclair, the conclusions drawn from the Sirtris substances show potential and results to date will be release in print in upcoming months.
All the excitement and anticipation around the sirtuin study including the solid scientific evidence, there is still no guarantee that the Sirtris Pharma meds will be effective. One of the lingering question marks surrounding the trials is whether caloric restriction is even something that will work for people.
Two authorities on senescence recently debated the question of the caloric restriction experience in the Journal Nature. They had misgivings that perhaps study results might be unsuspectingly deceptive when generated in lab mice. These rodents are chosen for their rapid reproduction and survive on a generous diet. A low calorie diet may be more suited to what the mice are used to when living in a feral state. The theory being their lives are extended simply because the lab diet is much healthier for them than what they would have consumed innately.
Prolonging life in lab organisms might not be the ideal since they are more likely to have a manufactured result. What of the impact caloric restriction has on short life organisms that have no worry of contracting cancer, unlike humans who are at greater risk simply by having a greater life expectancy therefore higher odds. Knowing these facts the argument is put forward that drugs that mimic caloric restriction could well just be a fantasy.
To decide if the caloric restriction model of longevity only works on “domesticated” rodents, what about testing on wild mice? Steven Austad from the University of Texas, Health Science Center has done just that. He concluded that caloric restriction did not increase the ordinary life span of feral mice, which lends credence to the theory that this methods value is only of benefit to mice in a lab environment. Still, others believe his conclusions can be translated in another way. One expert said the maximum life expectancy of wild rodents was lengthened and the experiment on caloric restriction was indeed successful.
Lab rodents are heavily cross bred and scientists often get varying results based on the breed that is used. In order to clear up the rodent information and make it consistent, the NIA or National Institute of Aging began a program that evaluated compounds via three laboratories at the same time. The first potential intervention contenders for age reversal were green tea extract and several doses of resveratrol.
The testing with resveratrol in currently running, however, recently the conclusions from different compound were released in print, the antifungal medication Rapamycin. It was discovered the Rapamycin extended the rodents lives considerably and that was after the mice were found to be the same as sixty year olds when the test commenced, this discovery was made by accident.
Rapamycin has no connection with caloric restriction based on research thus far, nevertheless, the investigation offered remarkable evidence that a chemical substance can indeed prolong life expectancy.
An additional conclusion linked to the caloric restriction method was discovered recently when a much anticipated trial on rhesus monkeys that were on the restricted diet. The study’s lead author was Richard Weindruch from the University of Wisconsin. Since primates are linked closely with humans, they would be an ideal test subject to determine if the rodent conclusions could be applied to humans. The results shown were vague at best.
The rhesus primates were on the caloric restricted diet for twenty years and were clearly in better condition than their non diet restricted brethren. They had less incidence of diabetes, cancer and heart disease. This verified that caloric restriction can ward off age related diseases in primates AND rodents as well.
When it came to life expectancy, the diet prolonged life considerably but only when scientists left out the fatalities that appeared to have no link to aging, like when they died under anesthesia [a requirement when drawing blood samples]. When all the deaths were calculated, life expectancy was not appreciably increased.
Some in the science community believe it is quite valid to pay no heed to these deaths. Some others believe that in the rodent trials, the number of dead rodents could be counted but the reasons for their deaths could be ignored. The same reasoning should take place with the monkey trials because who can be sure, whether or not a fatality occurring during anesthesia was an age related event or not.
Due to the results with the Rapamycin and the monkey conclusions, Dr Sinclair says there are fewer skeptics and more who believe the theory will become reality. He cited the capability of caloric restriction and sirtuin triggered drugs that could delay the diseases linked directly to aging, even if it was only in the mice. Even if the drugs eventually only spared humans the suffering from disease and there was no life extension, it would be a significant advance in anti aging medicine.
Individuals may well be living to such advanced years now that no drug would make a significant difference in their longevity. Given the success with less infant mortality and advances against numerous diseases, the life spans of humans, at least in developed countries, is increasing at a remarkable rate over the past hundred and sixty years or so. The life expectancy in women has increased from about forty five years old in 1840 to around eighty five years of age in the year 2000.
One major difference of opinion amongst scientists in the aging community is whether or not there is an inherent rate of aging. What if there were cures available for every disease known to humankind, would anyone ever die naturally? Some believe that there is a steady accumulation of damage done to DNA and the proteins such as collagen and elastin tissues that connect the body together. Damage done to DNA means control of genes becomes less accurate, causing a control drift that interferes with stem cells required to repair tissue damage. In the event that all disease could be eradicated, it is not apparent that there is anything that would be able to prevail over natural aging processes.
However, some experts think that there is no obvious difference that can be made between disease and the other fragilities associated with old age. Whatever a physician can bill for is considered a disease, though creased skin, grey hair or feeling lousy upon wakening each morning, these are not considered to be disease.
The very thought of natural aging is not understood very well and conversely to theories of those evolutionary biologists, there may well be fundamental methods for intervening in the progression of aging.
According to evolutionary biologists, life expectancy of various species is based on their adapting to their natural environment. For instance, feral mice might last a year in the wild since owls, cats and occasionally freezing to death are constant perils. Rodents with genetics that mean a longer life span can hardly ever be preferred by natural selection processes. It is those mice that are most fertile and leave behind the most offspring beginning at the earliest age possible that are favored.
Using this theory, if the rodents came with masks and capes, able to defy their natural enemies, they would be favored by natural selection for a prolonged life. Interestingly, the lifespan of bats is three and a half time greater than the flightless animals of the same size, according to yet another authority at the University of Maryland, Gerald Wilkinson.
Based on this perspective, cells themselves are so vigorous that there is no life span limitation. The problem is instead, keeping them regulated so they do not cause cancer, specifically in longer living species. Cells are not responsible for impeding the evolving, long term life spans, like those in the bristlecone pine tree, which lives for five thousand years, or even some deep water coral, some of which live for more than four thousand years.
There are certain species that appear to have an innate ability to live into perpetuity. The tiny freshwater animal called the hydra has the innate ability to continuously regenerate itself for nearly any part of its physical structure, due to an ability to not make a distinction between germ cells and normal cells within their body. In humans, the germ cells, the egg and sperm, do not experience senescence; babies are all born the same age, regardless of how old their parents are. The beginning of senescence was the splitting up of labor in the first multicellular animal linking the germ cells and the normal body cells.
This split put the burden of sustaining the species on the germ cells and the body cells were let loose to become specialized, as neurons or skin cells. However, when doing this the body cells became disposable. We die because, according to Thomas Kirkwood, an expert on the theory of aging, of the continuous effort that is necessary for body cells to keep going. He says that in the long term, this is unnecessary since – in terms of natural selection, there are more important things to do.
In the end, the only thing clearly understood about life expectancy is that it is fluid, it is not predetermined. There may indeed be methods to increase it.
Sat, Jan 30, 2010
Anti Aging, Anti Aging Theories, Bioscience, Longevity