Quick Notes from Quebec

 (or “Short Takes from Sherbrooke”),
Center for Research on Aging, Symposium Nov 2-4

Why does the cell appear to be shooting itself in the foot?” asked Andres Kriete of Drexel Bioengineering Dept.  All through the conference, I heard people puzzle that our bodies seem to miss opportunities to save themselves from aging, or worse, that they seem to be pouring gasoline on the fire.  Invariably, researchers sought to reconcile what they were seeing with their faith that the body really is evolved to protect itself as best it can.  Everything that looks on its face like a suicide mechanism is re-interpreted to have some hidden benefit.

I was invited to the conference as an advocate of programmed aging, the only one in the room.  I found everyone to be more than polite–listening with an open mind and eagerly engaging with me.  I spoke on a subject that I find exciting, and which has seen an explosion of results in recent months: the possibility that aging is controlled by a biological clock based on epigenetic programming.

 

Experts in diverse fields, hailing from La Jolla to Poland were represented, and I made several new friends, while renewing acquaintance with Siegfried Hekimi, whose lab I visited four years ago.  I woke up this morning visited by a muse, and penned this before I got out of bed.

Ballad of the Sherbrook Gerontologists

When joints and arteries become inflamed,
The body yields to nature’s conflagration
The standard culprit (as always) is blamed.
The problem must be some dysregulation

We scratch our heads, we wonder what went wrong.
To clearly programmed death we pay no heed…
And comfort find we in familiar song:
“Respect the body’s wisdom” is our creed.

The muscle’s satellites that proudly grew
Retire now and yield to cell senescence
Forsake their given mission, to renew…
But we question not their motives nor their essence.

We scratch our heads, we wonder what went wrong.
To clearly programmed death we pay no heed…
And find we comfort in familiar song:
“Respect the body’s wisdom” is our creed.

And even in the face of apoptosis,
The body’s good intent we must abide.
We tender our familiar diagnosis
And whisper not the phrase “cell suicide”.

For evolution is our benefactor
And we must never question her intent
We blame some tradeoff, or an unknown factor
Though on our own demise she is hell-bent.

We scratch our heads, we wonder what went wrong.
To clearly programmed death we pay no heed…
And comfort find we in familiar song:
“Respect the body’s wisdom” is our creed.

– JJM, 2014 Nov 4


Here are some teasers for things I found most interesting in this brief symposium:

One study in Scotland found diabetics who take metformin live longer than non-diabetics who don’t!  (There’s no data on non-diabetics taking metformin, because there are so few of us.  But in studies with normal, non-diabetic mice, metformin extends life span.) (from presentation of Nir Barzilai)


Centennarians don’t have healthy eating habits, don’t exercise more than others in their cohort or smoke or drink less.  They also don’t have genes that are associated with protection from cancer or heart disease or AD.  What they do have is genetic pre-disposition to long life, and it is specific genes that slow aging.  There are specific genes that are necessary to make to age 100, and without them your chances are slim.  (This is different from longevity between ages 70 and 90, which is affected much more by life choices, environment, etc.) (also from Nir Barzilai)


During the last 2 years of life of a centennarian, health costs are ⅓ what they are for the last 2 years of someone who dies at 75. (also from Nir Barzilai)


Burning ketone fuel instead of sugar helps protect the brain against Alzheimer’s Disease.  Fasting a few days, of course, shifts the body to ketosis.  A low-carb diet is ketogenic, but even better are medium-chain triglycerides, often refined from coconut oil for experimental diets. (presented by Alex Castellano)


The Free Radical Theory of aging has it all backwards, says Siegfried Hekimi.  ROS are not a cause of the oxidative damage that accumulates with age, but rather a signal that turns on the body’s protection against that damage.  In his McGill laboratory, worm life span has been increased almost twofold by exposing them to a strong pro-oxidant chemical.  In biology experiments, it is called “paraquat”, but the Vietnamese knew it as Agent Orange.  Of course, large doses of paraquat poison the worms, and their lives are shortened.  But a range of low doses is beneficial.  This result comports with genetic experiments.  The all-time record for long-lived, genetically altered worms is a worm that lacks the ubiquinone gene, so that its energy metabolism is completely disrupted and it is unprotected from ROS.


Children conceived to starving women in Netherlands 1944 had higher rates of metabolic syndrome 50 and 60 years later, due presumably to epigenetic patterns of methylation laid down at conception. (presentation of Irene Maeve Rea)


Michael Kobor of UBritColumbia shared my enthusiasm for the epigenetic clock. He cited recent work of Steve Horvath, demonstrating a set of epigenetic changes that are characteristic of the aging human.  Some of his own work documents the influence of childhood deprivation on epigenetics that affect health, psychology and longevity much later.


And in preparing my own presentation, I un-learned something that I been taught long ago.  DNA is supposed to be the same in every cell in our body (except for a small number of random mutations).  But a recent paper actually samples tissue from different organs and finds big differences.  Could it be that the body is re-configuring its own DNA, as well as epigenetics, when differentiating?  If this is real, it implies an ability we didn’t know cells possess.


Rumors are the most fun

Alan Cohen (from the home team at University of Sherbrooke) told me that he was in touch with Vaupel, whose work I wrote about back in January.  Vaupel had just published a paper comparing the aging patterns of 48 different animals and plants, mostly animals.  Some age gradually, some hardly age at all until the end, and they all die suddenly.  Some age “backwards” in that they become less and less likely to die as time goes on.  Alan told me that Vaupel and his group at Max Planck Inst have been expanding this list, drawing a more representative sample of 10,000 species, and there is a great deal more “non-aging” than anyone expected.


For at least 10 years, it has been known that senescent cells are “bad actors”, not just shirking their duty to the body but spewing out toxins that destroy neighboring cells and contribute to systemic inflammation, ultimately to cancer. In 2011, Jan van Deursen of Mayo Clinic in Minnesota published a paper that demonstrated this dramatically.  Mice were genetically modified to attach a self-destruct signal to the p16 gene, which is a marker of senescence.  The mice could then be dosed with a signal, and the senescent cells would eliminate themselves cleanly via apoptosis.  The mice with their senescent cells removed had a 20 to 30% greater mean life span and even better results for health span.  Even though these cells are less than 1 in 10,000, they do damage far out of proportion to their numbers.  (To my way of thinking, cell senescence is clearly part of the aging program.)

Van Deursen was there to explain and update his work.  The rumor is that there are at least five companies around the world working on drugs that will remove senescent cells without harming other cells, and that these drugs show promise for treating all the major diseases of old age.

8 thoughts on “Quick Notes from Quebec

  1. In your extensive guide of pills and supplement you talk about an alternate intake of aspirin and ibuprofen, do you have any study that show the benefetit of a daily dose of ibuprofen ?

    • There are many studies comparing NSAIDs for preventing heart disease, cancer and stroke. There’s no clear winner, and it may be that the best NSAID depends on you as an individual. Certainly if you have stomach problems with one, you should switch to a different one. Otherwise, you might mix them up. You can find these studies in PubMed by searching on NSAID, ibuprofen, cancer, heart disease, (in different combinations). I don’t want to recommend one study over another.

      Ibuprofen is antagonistic to aspirin, so alternating daily is not optimal. http://www.sciencedirect.com/science/article/pii/S0140673603125093

  2. “The Free Radical Theory of aging has it all backwards, says Siegfried Hekimi. ROS are not a cause of the oxidative damage that accumulates with age, but rather a signal that turns on the body’s protection against that damage…But a range of low doses is beneficial.”

    This is the theory of hormesis. Should I start smoking a cigarette per day?

  3. Quick question Josh,

    I just found your blog, but I wanted to ask you this. Have you had any luck over the past year or so with Product B? Any idea what the active ingredient is, or perhaps do they somehow work together somehow?

    Many of the ingredients I think can be likely bought from a Chinese or East Asian grocery store at a fraction of the price, although admittedly Product B does not appear to be very expensive either.

    • Product B is created by Isagenix with consultation from Sierra Sciences. Isagenix sends samples of various herbs and supplements to Sierra, and Sierra uses cell cultures to see if they turn on telomerase. To protect their trade secrets, they send the samples to Sierra labeled only by a code, so that Sierra doesn’t know what they are testing.

      Bill Andrews, head of Sierra Sciences, has told me that some of the ingredients that Sierra has tested for Isagenix are 50x more effective than cycloastragenol, which is said to be the active ingredient in TA-65. Remember that this is the result of a test in cell cultures, and says nothing about how well the product is absorbed from the stomach into the blood and thence into the cell. The ordering in the list of Product B ingredients is based on bioavailability rather than potency in the cell tests. The number one ingredient is silymarin=milk thistle extract, which is known to be poorly absorbed. Andrews has also suggested to me that the most potent ingredients are the LAST ingredients, included in smaller quantities in order to hedge the unknown factor of bioavailability and actual effectiveness in the body.

      As of last summer, Product B is available in a new formulation called Isagenesis, with a new changed ingredients list. The ingredients in the old version of Product B is here. I think the old version is still available from retailers.

      A context for this discussion is that there are probably no telomerase products on the market today that are strong enough to make much difference. Based on all I have read, I believe that no product now available can regrow telomeres as fast as they are lost in the course of normal human aging. Of course, we are all hoping that this may change.

  4. There is a recent interview with Michael Fossel on Singularity “Michael Fossel on Singularity 1 on 1: Compassion is the reason to reverse aging!” – where he is discussing about telomerase therapy o reset the DNA expression and he is touching this subject as well.
    He says that probably TA-65 is just about 5% as it needs to be a telomerase activator to be effective.
    I hope his research moves soon into human trials and hopefully will be effective! Might not be the perfect solution to slow/stop/reverse aging, but sure could be a step forward.

    Here is the link if anybody is interested to watch the interview:

    https://www.singularityweblog.com/michael-fossel/

  5. Where does that leave us then?

    Carnosine and possibly C60 bucky balls are potential hopefuls. How effectively does the body absorb L Carnosine?

    It’s likely that TA65, Product B, and similar products then are useless.

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