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Telomeres and Your Heart

Warning: this blog is not just regurgitation or rewording of a press release from somewhere else. It contains original content and original commentary.

Since February is National Heart Health Month, I thought I would update you on some recent advances in how telomere length interacts with the health of your heart.

Telomeres and the heart is a touchy subject for some.  There are still many doctors out there who just skim headlines and don’t read articles. When I am speaking to doctors, I still get asked this question, usually in a hostile tone: “Doctor (there is a certain way they say it that usually indicates they are cardiologists and I am just a lowly internist!), we know that the heart is postmitotic. How can telomere shortening account for dysfunction in a tissue that is not dividing and therefore not losing telomere length?”

Now, since you are probably not a cardiologist, let me tell you what that little paragraph means.

Certain tissues in the body do not divide and have extremely limited capacity to divide once they are fully grown. I say fully grown instead of “reach adulthood” because when you say adulthood it implies you are an adult and some tissues stop “growing” long before that.  And some continue to “grow” with their cells dividing into your twenties.  No matter how you define the above, the word postmitotic clearly means ‘stop dividing’.  This means that the tissue (heart and brain are the two best examples) cannot repair damage by cellular replication the way say skin and blood cells can.  Skin turns over every 72 hours and blood cells, depending on whether they are white or red, can turn over in hours or a few months.

The ability to divide gives the tissue a large repair capacity since it can make new cells to replace old damaged ones.  The postmitotic state of the heart and brain means they cannot repair the damage of say a heart attack or a stroke, and you are likely stuck with something permanent and bad if those tissues are damaged.

This is a huge oversimplification but the ability to divide and repair relies primarily on telomerase expression and a stem cell reservoir.  It turns out that heart and brain, like most other organs in the body, have them both but in smaller numbers, amounts and with an increased suppression of telomerase.  This means that unlocking those things — telomerase and stem cells — could potentially regenerate even these “non-repairable tissues”.

Here is where my cardiology colleagues usually blow it.  They actually forget what they are treating.

I ask, “What are you treating in a heart attack?”  The answer is usually something like, “The heart muscle, you idiot!”

Wrong! Other than the few cardiologists who actually use Coenzyme Q10 in their patients, there is not one drug for long term treatment of heart muscle.  Luckily, the heart muscle is not the problem. The blood supply to it is, so you are actually treating the blood supply to the heart muscle, the coronary arteries. And no one debates that blood vessel health function and aging is very much telomere dependent. So as the blood supply to the heart and the heart ages, gets damaged and dies.

Case closed?  Well sort of!

That is only half of the story. You see, God, the universe or Mother Nature if you prefer, gave the human cardiomyocyte (heart muscle cell that does the pumping) longer than average telomeres, at least in those cases where we’ve been able to look at them.  This means that the heart might be more resistant to telomere loss than other tissues. Why would that be the case?

Well, oxygen, the essential element in air that keeps us alive, is a dangerous friend. Why?  Because it can oxidize biologically active molecules by forming free radicals.  The heart is the very first tissue to see that most highly oxygenated blood – so having longer telomeres would be a good thing, giving the heart a little extra mileage in terms of longevity.

Unfortunately we humans have figured out many ways to shorten those telomeres faster than normal.

Here are the usual suspects: a diet rich in inflammatory Omega 6 fats and low in Omega 3 fats, lack of sleep, stress, lack of or too much exercise, a nutritionally poor diet lacking vitamins minerals and antioxidants.  All of this helps speed up the loss of our telomere biologic time clocks in all cells, not just the heart.

But there is still one more piece of the puzzle and this is the really cool part.  Over the past decade or so a huge project looking at the human genome, called ENCODE, has been going on. This is part of the reason why epigenetics has become a hot topic.  But just as epigenetics was hitting its stride as the du jour household word, information came out about a bunch of other “factors” that influence how our genes are read.   As a reminder, we age not because of changes in our genes, but how our genes are read, so pay attention here.

One of several “new” (new here meaning not commonly known by the public!) messengers have been discovered. One of them is call miRNA short for micro RNA. If you remember high school biology, RNA is the stuff that you make from “reading DNA, the genetic blue print”. That RNA usually goes along and gloms on to some protein factory somewhere and some enzyme or other messenger protein is made.

Not so with miRNAs. Their function is strictly to turn something on and off. As far as we know, they don’t ‘make’ anything.

OK, now back to the heart. An miRNA was recently discovered called miR-34a.  MiR-34a is associated with two big things: an aging heart, which makes more of it and MI’s, more commonly known as heart attacks. Once again, this is a gene off/on signal that rises with aging and changes which genes are read and how.

If you block the production of this particular miRNA or its target called PNUTS, you reduce heart cell death rate following heart attack and you reduce scarring. You also reduce the age-related decline in heart function.* How?  By reducing the end point of all this, which is telomere shortening in the heart.  So all this great new stuff points once again to our old friend the telomere as the central actor in determining who lives and who dies in the heart and otherwise!

Another why: because the telomere governs the damage response of the cell and whether it lives, senesces (slow death) or explodes from the inside out (apoptosis). And heart telomeres get shorter just like any other telomere! And because they normally express absolutely no telomerase, they are even more susceptible to telomere loss even if they start out with longer telomeres than other tissues.**

That is enough science for today but let me sum it up even more simply for you.

Heart disease is the number one cause of death in this country.

Telomeres rule!

Take care of your telomeres.

Don’t forget your fish oil and TA-65.

Happy Healthy Heart Month!

 

Doc

* This is still at the laboratory level and has not been tested in living people!

**Well established norms for telomere length in various tissue types have not yet been explored fully.

Reference:

MicroRNA-34a regulates cardiac aging and function

2 replies
  1. dennis
    dennis says:

    The below Mayo Aging conference showed The key to slowing cell senescence is inhibiting mTOR. (mTOR) is a protein that regulates cell growth, proliferation, motility (ability to move food through its digestive tract), survival, protein synthesis and transcription (the first step of gene expression). If you’ll look over these functions, you’ll see why inhibiting mTOR is a key to treating cancer and probably preventing many cancers.

    According to Dr. Watson, 80 genes are regulated and changed, and eleven factors contribute to mTOR inhibition. As far as he can determine, the only compound that addresses all eleven is low doses of the drug rapamycin(side effects very bad). TA65 only only addresses one of the eleven factors in the presentation below. Any of the other 11 factors can cause cell senescence and aging.

    http://www.ustream.tv/recorded/29212931

    Reply
    • Dr Dave Woynarowski
      Dr Dave Woynarowski says:

      The Mammalian target of Rapamycin is an important regulator of protein synthesis including telomerase but mTor levels are conversely sensitive to telomere length, giving us a chicken or the egg phenomenon. For me, the proof is in the pudding. Ongoing high level expression of telomerase extends mammalian life span in ways mTor inhibition does not and what you will see when the final studies are released is that all of the metabolic regulatory pathways including mTor, FOXO, and sirtuins and mitochondrial function all respond to telomerase activation in a positive fashion. As of yet, no one has a safe enough mTOR inhibitor to extend longevity on a repeatable routine basis. TA-65 is also a supplement, not a drug. It is highly unlikely that any Rapamycin-like analog will be available to the general public for longevity/healthspan purposes during either of our lifetimes.

      Reply

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