Tuesday, November 27, 2007

Telomerase Activation Redux

Founder of T.A. Sciences Noel Thomas Patton read my recent blog post entitled Ending Old Age through Telomerase Activation, and called me on the phone to offer his feedback. Specifically, he made a point of questioning the accuracy of my claim that "there are many cell types in the human body that never stop reproducing," and he was right to do so. The only healthy cells in the human body that do not eventually become post-mitotic are germ cells, and the only way that germ cells remain immortal is by being passed on to one's descendants through sexual reproduction. Even stem cells will eventually "run out of gas" and become post-mitotic if organismal senescence does not kick in, albeit through a telomerase independent senescence mechanism, which is why I am convinced that telomerase therapy is the first and most critical step on the path to immortality.

Patton and I talked for the better part of an hour, and more than once he qualified his assertions regarding the small molecule telomerase activator known as TA-65 [PDF] (which T.A. Sciences has licensed from the Geron Corporation) and the potential benefits of the Patton Protocol with the statement, "I am not a scientist." Truth be told, my somewhat eclectic resume would not qualify me as a scientist per se, but that doesn't stop me from saying with a great deal of scientific certainty that any regimen of nutritional supplements comes with inherent health risks, and the Patton Protocol is no exception. Even so, the risks are minimal at this time, and if I were 75 years old, I'd say that the risks were negligible; I'd even be willing to go tens of thousands of dollars into debt to pay for the Patton Protocol at that age. Moreover, if I had a child who was suffering from a premature aging disease like progeria, I would say that the potential benefits of giving that child TA-65 as a dietary supplement far outweighed any of the financial costs or potential (and as of yet unobserved) side effects. However, I am hard pressed to believe that anyone else under the age of 50 would substantially benefit from such a regimen, a fortiori if his or her father or grandfather lived past the age of 80.

Although he is "not a scientist," Patton suggested that someone in his or her 40s would benefit substantially from the Patton Protocol, and that the only contra-indication he could think of would be the potential for cancer in certain individuals. Of course, another reason not to go on the Patton Protocol at this time is the fact that a year long regimen of TA-65 currently costs $25,000.00. Even if your net worth is in excess of ten million dollars, that's a lot of money for a nutritional supplement, a fortiori if you are not suffering from any age-related medical conditions. On this note, one of the great luminaries in the field of rejuvenation research is Michael J. Fossel, M.D. whose interest in the field was sparked by his work with children suffering from progeria. Back in 1997, Dr. Fossel accurately predicted that human trials of telomerase therapy would begin in the next ten years, and that victims of progeria would have little to lose from such treatment in terms of life expectancy and everything to gain. Unfortunately, the Patton Protocol cannot be tested on such individuals without dealing with an enormous amount of government red tape. Just one more example of your tax dollars, hard at work.

Patton made a point of downplaying the notion that TA-65 might be the key to immortality. However, if TA-65 does in fact activate telomerase systemically throughout the human body, and thereby lengthens the telomeres at the end of DNA strands, then it is without a doubt a key ingredient of the philosopher's stone. Beyond that, I think it's safe to say that the next major scientific challenge of rejuvenation research will be overcoming the problems that arise from deleterious mutations of mitochondrial DNA. And beyond that, I'd say that medical science has a century or two to figure out what the next major challenge of rejuvenation research will be and how to deal with it.

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Friday, November 23, 2007

Ending Old Age through Telomerase Activation

When I took my first college level course in physical anthropology, I took it upon myself to research the emerging body of scientific knowledge regarding the biological process known as senescence. Simply put, many (but not all) biological organisms grow to maturity, then attempt to maintain vitality, but eventually succumb to the ravages of old age and die. The process through which such organisms lose vitality is what is known as senescence.

Scientists have long believed that human aging is genetically programmed, and studies have more or less confirmed the fact that organismal senescence in humans is caused by senescence that first occurs at the cellular level. To wit, as humans age, the various cells in their bodies slow down the process of mitotic reproduction through which dead and damaged cells are routinely replaced. Eventually, this process stops altogether as cells reach what is known as their Hayflick limit and become "post-mitotic." Consequently, vital organs fail, and humans die. But for many years the question remained: Why do human cells become post-mitotic?

The Hayflick limit is not universal among all cell types. In fact, there are many cell types in the human body that never stop reproducing, and there is a general consensus among scientists that the key to what makes certain cells immortal is a naturally occurring enzyme known as telomerase. This enzyme works to repair the ends of DNA strands, known as "telomeres." Telomeres contain no genetic information. Rather, they are like the protective plastic tips that are found on the ends of shoelaces. Other things being equal, telomeres become shortened through the process of cellular mitosis, and when they become too short to insure the integrity of the DNA strands they protect, the cells containing those DNA strands become post-mitotic.

Since at least 1995, scientists have been working on ways to activate telomerase in healthy, post-mitotic cells, and they have already done so with both mice and human tissue. The undisputed leader in this field is a company called Geron, and many people (including me) have been waiting patiently for Geron to begin human trials. That wait came to an end in April of 2007 when a company known as T.A. Sciences under license with Geron published their findings of human trials involving one of Geron's products known as the TA-65 molecule.

Among those who have been following the still developing story of the human trials of TA-65, there's been quite a bit of speculation as to what the TA-65 molecule is. Adding to the confusion is the fact that the trials used TA-41, a TA-65 precursor molecule. According to T.A. Science's Executive Summary, TA-41 is an astragalus extract, astragalus being a plant (somewhat obscure in the West) that has been used for centuries in traditional Chinese herbal medicine. But whatever TA-41 or TA-65 is, the claims made regarding its anti-aging properties are nothing short of phenomenal. To wit, 2 to 4 daily doses of 10mg tablets of TA-41 were given to men aged 60 to 85 for 12 weeks in a double-blind study, and the condition of their immune system, eye sight, sexual function, and skin improved dramatically.

Based on the results of these human trials, T.A. Sciences is now offering a year long regimen of TA-65 for the not-so-low price of $25,000.00. Not all of this fee is paid up front. Rather, a baseline testing of various aging biomarkers is performed for $2,000.00, and three weeks later an independent doctor gives you a private consultation of the results for $500.00. If you decide to move ahead with what they are calling the Patton Protocol, you then pay $11,250.00 for the first six months; at the end of six months, the tests performed in the baseline are repeated, and you pay another $11,250.00 if you want to continue with the program. Beyond that, there is vague discussion of "a possible continuing TA-65 program" at a reduced cost.

While it seems too good to be true, there is a distinct possibility that the Patton Protocol may actually succeed in halting and reversing the aging process in human beings through telomerase activation at the cellular level. I say this as someone who took various classes in physical anthropology and earned a bachelor's degree in anthropology before attending law school. In the meantime, I've kept pace with various scientific studies of senescence, observed the discovery of the role that telomeres and telomerase inhibition play in the process of cellular senescence, and then waited patiently for human trials of telomerase therapy to begin. And I can honestly say that I never thought it would come in the form of a nutritional supplement.

Is telomerase activation the key to a potentially unlimited human lifespan? It's too soon to tell, but as an anti-aging regimen, it's the most promising I've seen. And once the data is in on the Patton Protocol, scientists can explore the possibility that there are alternative and/or additional causes of aging such as the degradation of mitochondrial DNA that may end up being just as deadly to humans as shortened telomeres.

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Monday, November 12, 2007

Being Too Smart for Your Own Good

While exploring the website of the Singularity Institute for Artificial Intelligence, I was guided to an essay by Eliezer Yudkowsy entitled Cognitive biases potentially affecting judgment of global risks. [PDF document]. I experienced several "A-ha!" moments while reading the essay, all of which synchronized with my inherent skepticism of supposed expertise. And at the risk of sounding like I am ignoring Yudkowsky's warnings, I knew it all along.
"The systematic experimental study of reproducible errors of human reasoning . . . is known as the heuristics and biases program in cognitive psychology. . . .

"[ . . . ]

"The . . . program has uncovered results that may startle and dismay the unaccustomed scholar. . . .

"[ . . . ]

" . . . [B]y making you a more sophisticated arguer . . . I have actually harmed you; I have made you slower to react to evidence. I have given you another opportunity to fail each time you face the challenge of changing your mind. . . .

" . . . Awareness of human fallibility is a dangerous knowledge; if you remind yourself of the fallibility of those who disagree with you. If I am selective about which arguments I inspect for errors, or even how hard I inspect for errors, then every new rule of rationality I learn, every new logical flaw I know to detect, makes me that much stupider."
Yudkowsky narrates a number of scenarios where experts are inclined to convince themselves that they know more than they actually do, particularly when it comes to overconfidence in their estimates, then points out that he has barely scraped the surface in uncovering the astonishing number of ways that so-called experts can be wrong. He then goes on to admit his own arrogance in estimates that he once made regarding the development of Artificial Intelligence by 2025, with a peak in 2018.
"Why did I ever think I could generate a tight probability distribution over a problem like that? Where did I ever get those numbers in the first place?"
I am reminded of a joke that was once told to me -- i.e., that 90 percent of all statistics are made up on the spot. In accord with this joke, I am inclined to dismiss virtually all statistics as irrational appeals to authority. At the same time, I am inclined to interpret Yudkowsky's predictions regarding the development of Artificial Intelligence as harmless wishful thinking. Of course, making this sort of excuse for an expert that I like is one of the cognitive biases that Yudkowsky warns against, so I guess I'm part of what I have always referred to as the "ongoing worldwide conspiracy of ignorance and incompetence."

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