For decades, many scientists have believed that the theoretical 125-year limit on human lifespan, and the decline in our health in old age, is imposed by the gradual shortening of our telomeres. Telomeres are structures at the ends of our chromosomes that shorten with every cell division, and telomere shortening has been theorized to be the "clock of aging" contained within the human body. Evidence has been mounting that this hypothesis is correct, and in 2009, the Nobel Prize in Medicine was awarded to scientists who originally characterized telomeres and telomerase. However, Dr. DePinho’s research is possibly the strongest proof of concept for this hypothesis yet.
This research was built upon earlier studies and experiments on mice. In the wild, mice do not age the same way as humans; they produce telomerase throughout their lives and generally die because they are lacking several important defenses against oxidative stress that humans possess. However, since 1999, it has been possible to disable the telomerase gene in mice. After breeding telomerase-deficient mice for six to seven generations, scientists have been able to create strains of "telomerase knockout" mice that do age like humans, and show classical symptoms of human aging including graying hair, frailness, spontaneous malignancies, etc.
In Dr. DePinho’s experiment, instead of disabling the telomerase gene, his team constructed a version of telomerase that is completely inactive until it is introduced to the drug 4-hydroxytamoxifen. They created a line of mice with this altered form of telomerase, and then bred them for several generations, until the telomeres of these mice became short enough that they began to display human-like symptoms of aging. Then, they introduced 4-hydroxytamoxifen to the mice, activating the telomerase in their cells.
The team found that this treatment successfully decreased the abundance of cells with critically short telomeres in these mice. More significantly, this allowed resumption of cell proliferation, and eliminated the symptoms of degeneration across multiple organs, including the testes, spleens, and intestines. It also reversed neurodegeneration in the mice, causing proliferation of new neurons and increasing the animals’ brain weight. These were results that, if seen in elderly humans, would constitute a successful reversal of the aging process.
Human cells are capable of producing telomerase, but do not do so under most circumstances. We possess a genetic "switch" that controls expression of telomerase, but, unlike the mice that were altered to respond to 4-hydroxytamoxifen, we don’t know exactly what chemical turns telomerase on in our bodies. However, over the past eleven years, Sierra Sciences’ research under the leadership of Dr. Bill Andrews has led to the discovery of 38 distinct drugs that cause some de-repression of the telomerase gene. Further medicinal chemistry should enable the discovery of the exact chemical that turns on telomerase in humans.
Sierra Sciences has also developed mechanisms for screening thousands of natural products a week for telomerase induction, and expects to be able to launch a nutraceutical that turns on telomerase in humans by early 2011. Dr. Andrews and Sierra Sciences have entered into a partnership with John Anderson, founder of Isagenix, International and CEO of Dream Master Laboratories, a manufacturer and formulator of natural products, to quickly bring this nutraceutical to market.
"Telomere shortening has a role in a vast number of diseases," said Dr. Andrews. "We see telomere shortening as a primary culprit in everything from atherosclerosis to osteoporosis to macular degeneration; really, any disease you’re more likely to suffer from at age 70 than age 30 probably has something to do with telomere shortening. Just as telomerase activation reversed degeneration in the organs of these mice, we expect that it can do the same for humans. Telomerase activation technology promises to be the most significant advance in human health since germ theory."
Significantly, the mice in Dr. DePinho’s experiment did not suffer from an increased risk of cancer over the four-week course of their treatment with 4-hydroxytamoxifen, and inducing telomerase increased the median survival of these mice over that four-week period. It has been hypothesized that telomerase activation in humans could lead to cancer, but that hypothesis has never been experimentally validated.
"This study is really just another nail in the coffin for the idea that telomerase induction would lead to cancer," said Dr. Andrews. "Even as early as 2002, a review of 86 publications showed that telomerase is not a carcinogen or oncogene. And research within the past two years has shown that short telomeres are actually a very significant risk factor for both the incidence and the mortality of cancer, and that lengthening telomeres by inducing telomerase should actually prevent cancer.
"It might have once seemed intuitive to suggest that, because 85% to 95% of cancer cells express telomerase, telomerase was a cause of cancer," Dr. Andrews said. "But, now, the evidence is in, and it’s become absolutely clear: telomerase does not cause cancer. Cancer causes telomerase, but telomerase does not cause cancer."
ABOUT SIERRA SCIENCES
Sierra Sciences LLC (www.sierrasci.com) is a company devoted to finding ways to extend our health span and lifespan beyond the theoretical maximum of 125 years. Sierra Sciences was founded by Dr. William H. Andrews to continue his anti-aging research and to commercially exploit the results by developing a pharmaceutical to prevent and/or reverse cellular aging. We are pursuing basic research to develop a pharmaceutical that will cause the endogenous telomerase gene to express an enzyme called telomerase which has been shown to extend telomeres, thus restoring cells to youthful vigor.
SOURCE Sierra Sciences, LLC