The Immortalizing Enzyme

In the early 1500s, according to legend, the Spanish explorer, Ponce de Leon, traversed Florida looking for the Fountain of Youth. He never found it. 500 years later, scientists are still searching for it. They haven’t found it either, but they might be getting close.

A certain anti-aging enzyme has captured the attention of the scientific community. Telomerase is the name of this “immortalizing enzyme.” There is no publicly traded company doing real telomerase gene-activation research now. Moreover, there is no guarantee that those who are working in this area will accomplish their goals of stopping or reversing the cellular aging process.

This is, however, an area that investors in transformational technologies should be monitoring closely. So consider this a heads-up.

In the last 100 years, improvements in medical technology have had an enormous impact on life expectancies. In America, life expectancy has gone from 47 years in 1900 to 78 years today. Although life expectancy has improved, the maximum human lifespan of 125 years has not. Few of us make it that far, of course.

Big things, though, are happening in regenerative medicine and anti-aging technologies. Clinical evidence is mounting that one of the most important mechanisms of human aging, telomere shortening, can be arrested or even reversed with drugs that induce telomerase production.

Telomerase is the enzyme that regenerates telomeres. Telomeres form the end pieces of our DNA strands in chromosomes. Without telomerase, telomeres shorten every time a cell divides. As we age, cumulative divisions increase, and the length of the telomere caps decreases. Eventually, the strands get too short to permit cells to divide and regenerate accurately. Cells become senescent – old. Eventually, when enough of our cells become senescent, we die.

Therefore, if we could somehow lengthen the telomeres in human cells, we could theoretically greatly increase human lifespan.

The potential of telomerase-activating compounds, therefore, extends far beyond lifespan extension. Studies show that short telomeres are a risk factor for diabetes, Alzheimer’s, atherosclerosis and cancer. When the cells lining our blood vessels break off because of turbulence in the bloodstream, other cells have to divide to replace them. The replacement cells, of course, have shorter telomeres. Studies have found that the parts of the circulatory system that have the most plaque buildup also tend to have the shortest telomeres.

Alzheimer’s has also been shown to have a connection to telomere length. Although causality has yet to be determined, the brain cells of Alzheimer sufferers are shorter than those who do not have the disease.

Until recently, most scientists believed it was impossible to halt or reverse the molecular aging that takes place inside of our cells. That began to change with the publication of a paper detailing a study done by Geron Corp., Sierra Sciences, T.A. Sciences and the Spanish National Cancer Research Center.

The paper describes the activity of TA-65, the first compound discovered that activates telomerase in the human body. T.A. Sciences, based on licensing from Geron, markets TA-65. Geron is the original discoverer of the compound. TA-65 is derived from the roots of Astragalus membranaceus, a plant used in traditional Chinese medicine.

But TA-65 is a relatively weak telomerase-activating agent. The question, therefore, is, “What would a strong telomerase inducer do?” Specifically, many scientists wanted to know if telomerase could merely slow the aging process, or whether it might actually turn back the clock.

The journal Nature recently published an article showing that telomerase reverses the aging process in mice genetically engineered to lack the enzyme. The study was carried out by scientists at the Belfer Institute for Applied Cancer Science and various departments of Harvard Medical School.

Let me explain the purpose of the study by quoting the source. This is a little technical, but it is worth reading carefully:

An aging world population has fueled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged.

To find out if these dramatic effects are reversible, Dr. Ronald DePinho’s team engineered mice with the telomerase inactivated in such a way that it could be turned back on by feeding them the chemical 4-OHT. The researchers allowed the mice to grow to old age without the enzyme, and then reactivated it for a month.

Nature News reports the following: “What really caught us by surprise was the dramatic reversal of the effects we saw in these animals,” says DePinho. He describes the outcome as “a near ‘Ponce de Leon’ effect” – a reference to the Spanish explorer Juan Ponce de Leon, who went in search of the mythical Fountain of Youth. Shriveled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver and intestines, recuperated from their degenerated state.

The one-month pulse of telomerase also reversed effects of ageing in the brain. Mice with restored telomerase activity had noticeably larger brains than animals still lacking the enzyme, and neural progenitor cells, which produce new neurons and supporting brain cells, started working again.

“It gives us a sense that there’s a point of return for age-associated disorders,” says DePinho. “Drugs that ramp up telomerase activity are worth pursuing as a potential treatment for rare disorders characterized by premature ageing,” he says, “and perhaps even for more common age-related conditions.”

Over the past decade, Sierra Sciences has been working on finding more potent telomerase-activating compounds. Laboratory tests reveal that several of these molecules have 100 times the potency of TA-65. These, however, are man-made molecules and would require many tens of millions of dollars to obtain regulatory approval.

Currently, the company is looking at naturally occurring substances because they would be easier to bring to market than a man-made drug. Sierra Sciences has discovered various natural compounds that increase telomerase production, but it is not yet clear if they will increase telomere lengths.

Telomerase research is still in the early stages, but the financial implications of success at extending life spans through regenerative medicine would be unfathomable.

Time is the one product for which there is unlimited demand.


Patrick Cox,
for The Daily Reckoning

The Daily Reckoning