A Unified Theory of Aging Part 6

ta-65-and-bonus_256I have written several emails/blogs etc in the past dealing with health, disease and now aging. Since there were 5 prior writings dating back to 2004 and culminating with the most recent “Is aging unstoppable”.  I decided to name this one appropriately “Part 6”.

This is also a reminder to you that have been doing this a long long time. You could say I’ve grown old doing it except for the objective lengthening of my telomeres and the young looking bone marrow I have now that I did not have even 6 years ago!

Now it may not seem it from what I about to write but there is some major simplification going on here-enough to make any PhD in molecular biology break out their Dr Dave voodoo dolls and start pinning my effigy to the wall next to their favorite pentagram.

But in the simplicity of it lives the honesty as well.

So here it is.

If you really want to drill deep down into the aging process and more importantly how to fix it you have to look at DNA damage, the DNA repair and damage responses and yes, you have to remember that those little biologic time clocks we call telomeres are part of that DNA, and thus subject to damage and repair as well.

It wouldn’t hurt to remember that they are also “different” from genetic DNA in that they are somewhat isolated at the end of the chromosome and rather densely “protected” from the typical repair processes. So much so that they need a repair system of their very own which has been name “telomerase”.  If you’ve read any of my TA-65 writings then you know that telomerase is the enzyme that is activated by TA-65 resulting in a reduction of critically short telomeres, and in the one human study ( and multiple mouse and cell line studies) has resulted in reversal of some of the markers of aging including the all important reversal of immune system aging.

With all that in mind protection of all your DNA especially your telomeres is a really really good idea.

But how?!

If you look at the main causes of DNA damage, they would include UV and IR radiation, chemicals (more familiar to you as “toxins”!) and life style choices that accelerate free radical generation including lack of sleep, poor diettoo little or too much exercise and of course stress. So you should already be concluding that addressing these things to the extent that you can, will slow down the damage to your DNA and may help you live longer. If you need a refresher on this get our book The Immortality Edge!

You’d have to also look at what is often called Replication and Repair Infidelity of DNA. The first of these to R n’R’s occurs more frequently than you might think: somewhere between one in every million base pairs and one in  every billion base pairs. This doesn’t sound like much but consider that the average human genome has over 6 billion base pairs and that DNA is replicated pretty darn often and all of a sudden it looks more ominous. But that is where the repair fidelity (the second of the R ‘n R’s) comes in. Because we know the spontaneous mutation rate of DNA is lower than that of the number of replication mistakes, we can conclude there is a high fidelity proofreading and repair system at work. But it’s not perfect! If the repair process screws up and you get a faulty repair job. This can wind up being a mutation that does something usually bad or it can initiate the damage response and remove the offending DNA and its surrounding cell from the cellular pool by blowing it up (apoptosis) or just making sure it doesn’t replicate (senescence).

Do how do you improve DNA R ‘n R fidelity? Well the truth is you can’t. But you can at least not make it worse by generating more free radicals with all those life style choices we talked about a few moments ago. Trust me; the acceleration of this process is far more dangerous than the inherent infidelity of it for most of us!

Now let’s look separately at telomeres and telomerase. The biologic time clock function of the telomere hits a lot of other places in your cells as does the presence or absence of the enzyme telomerase. Recall that most cells have no telomerase expression, it’s completely shut off.  In very rapidly dividing cells or cells that need to maintain DNA integrity (so the genes are not messed up) telomerase is turned on to some extent.

The “lymphoid” or white blood cells which we will super simplify and call the major immune cells, are one of the few compartments where telomerase is required for continued function of that system.  Other notables include stem cells which provide the repair function of most tissues in varying degrees and germ line cells which keep us alive as a species by becoming sperm and eggs!

In terms of aging the integrity and function of our immune system and our stem cells are the major things that determine our aging processes. You might want to take note that the immune system is also highly dependent on stem cells for the constant supply of “body defenders” we need to live in this hostile environment we call planet Earth!

I should also point out that a couple of things that jump out at you if you follow the research on telomere length and telomerase activation including TA-65 are: improved immune function, improved wound repair and no increases in cancer.

Finally I want to touch on the cellular powerhouses known as the mitochondria. One criticism of the “telomere theory of aging” is that it does not address slowly dividing tissues like heart or brain.

If you look at aged heart and brain cells they do indeed have shorter telomeres. Probably more importantly and often forgotten is that the blood vessels that feed them have a more rapidly dividing lining that is telomere-aging dependent.  A tissue that doesn’t get blood gets sick and dies!

But let’s forget that for one second because if we make a “rule” of theory we have to explain everything no exception. Well, it does not matter if they are shorter because of cellular replication as in rapidly dividing tissues or because of free radical damage from all the things we just talked about above- the telomeres get shorter either way!

Recent work looking at the DNA damage signals thrown off by shortening telomeres shows a series of signals that ultimately affect the mitochondria in bad ways. Those bad ways include: decreased function, increased DNA damage and mutation to mitochondria DNA, and decreased new mitochondria and finally leaky mitochondrial membranes that are the hallmark of cellular senescence and aging!

All of that leads to impaired power generation in both highly replicative tissues and aging tissues. If you remember what I just said about immune cells and stem cells you will see how those 2 very critical cell lines are affected in this somewhat indirect but important way by telomere loss and damage.

You will also understand why I have said several times before that “aging is an inflammatory process which may be accelerated by telomere loss”.

Ok so by now you are saying, “I get it doc don’t get old!” A few scientists who will not admit they are even reading this blog are attaching my name to expletives and complaining about how “telomere centric” I am.

Here’s the thing. Telomere loss and damage may not be the only thing that causes aging. It may or may not be the major thing. But it is the clearest pathway to slowing or stopping the aging process we have ever identified. It crosses all the cell lines that are important for preservation of our species and of ourselves.  Telomerase activation has increased the life span and health span of mice modeled to mimic human aging and accepted by scientists the world over as valid models.  And in one human study with TA-65 it has led to improvements in health parameters and a decrease in the percentage of short telomeres that are known to drive the aging and disease process in people.

You got something better?




DNA Replication Fidelity*

  1. Thomas A. Kunkel

+Author Affiliations

  1. Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709

The Maintenance of Mitochondrial DNA Integrity—Critical Analysis and Update

  1. Mikhail Alexeyev,
  2. Inna Shokolenko,
  3. Glenn Wilson and
  4. Susan LeDoux

+Author Affiliations

  1. Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama 36688

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