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Nickola from Singularity Webblog has a new interview with Dr. Michael Fossel, an expert on telomeres and telomerase. Quite an interesting interview. He has a new book, called the Telomerase Revolution and new company, called Telocyte, focused on extending telomerase to lengthen telomeres, and he claims, slow & reverse aging. Pretty big claims, and honestly he came across in the interview as a bit of a salesman...

 

Unfortunately I can't seem to embed the video to start up at specific times, so I'm going to list the times of a couple interesting sections in the video, so you can jump ahead manually in the video embedded below:

  • At 16:25 Nickola reads a single sentence summary of Fossel's "Telomere Theory of Aging" from his book.  - He's basically saying that aging is a programmed result of changes in gene expression as the organism gets older, orchestrated by telomeres. When the relative length (not absolute length, he's clear to point out), of telomeres shortens, it changes which genes and especially how quickly genes get expressed, i.e. get read and translated into proteins. Without the right protein mix, bad things happen in cells, or more specifically, bad things continue to be generated, but they are no longer broken down at a fast enough rate. So they accumulate, and that is the major cause of cellular aging. So things like beta amyloid, or advanced glycation end products (AGEs), which can be broken down effectively in young animals, accumulate when telomeres get short and proteins aren't created to break them down.
  • At 24:20 Fossel talks about why (teleologically) he thinks we age. That is, if its possible to keep the protein mix in cells "young" (via telomerase or some other method), why doesn't the body do this all the time? I was thinking he was going to say it's a tradeoff with cancer. But no, he doesn't. He says (to paraphrase) we age because the quicker a population turns over, the quicker it can adapt to a changing environment. For example, viruses that reproduce quickly can adapt very quickly via mutation. So organisms are designed to die off so that their mutated progeny can inherit the earth (or at least their parent's niche). I'm pretty dubious of this model... It doesn't seem to jibe with the "selfish gene" theory which seems pretty well established. But what do I know...
  • At 33:40 and again at 40:30 he talks about the effectiveness (or lackthereof) of existing telomerase activator compounds, particularly astragalus. He says there is some evidence it works, but the supplements are either really expensive (like $200/mo) from reputable companies, or likely contain little astragalus if they are a lot cheaper. Josh Mitteldorf talks about telomerase and astragalus in several posts, like this one about a guy who has been taking high doses of astragalus since 2007.
  • At 36:00 Fossel talks about the data in animals that suggests resetting telomere length can reverse aging as measured by quite a number of biomarkers.
  • At 42:40 he talks about the potential side effects of lengthening telomeres, and specifically cancer. He makes an argument that cancer is unlikely to be significantly increased, but acknowledges there is the possibility that it would. His argument that it won't cause cancer is that extra telomerase upregulates expression of genes that repair DNA, so that will reduce cancer rate, balancing out with the extra ability for cells to divide.
  • At 46:00 he says that's one reason they are targeting Alzheimer's Disease in their first clinical trial, because AD is a death sentence and these people are old anyway, so cancer won't have that long to proliferate and spread even if it is slightly increased by telomerase therapy.
  • At 48:15 he talks about Liz Parrish and her "N=1" experiment with gene therapy, including telomerase activation. He understands her frustration with the slow progress of anti-aging research, but he is pretty skeptical that we'll be able to learn anything from her, because she is so young and healthy. He says she'll basically have zero credibility because of the way she's gone about it, without oversight, FDA approval, etc. He says they are going to go through the right FDA clinical trial process with their own efforts, at Telocyte.
  • At 58:00 he talks about Aubrey and "longevity escape velocity". He says people 100 years from now will look back and identify the coming decade as the time frame when we cured aging. He says at 1:01:15 that there will be an "inflection point" that dramatically slows aging, whether you want to take the therapy or not, and whether there may be side effects or not, and that breakthrough will occur in the "next few years". He also disses Aubrey as not quite understanding the genetics involved in aging, and therefore being too conservative"by mistake", both in the timeframe for curing aging, and in the value of telomere therapy...
  • At 1:02:00 he talks about the biotech company he started last year, Telocyte. They are planning a clinical trial to show they can "prevent and cure" Alzheimer's disease. If things go really well, he hoping to start a phase 1 clinical trial with a handful of AD patients around the end of 2016, have results 6 months later, and hopefully phase 2 trials shortly after that, if the phase 1 goes well. At 1:06:30 he talks about the clinical trial timeline in detail.
  • At 1:10:20 he fields a question about how telomerase therapy can (or can't) deal with the other types of damage that accumulate with age. Like lipofuscin. He says "no problem", longer telomeres should do the trick. Not an entirely satisfying answer...
  • At 1:15:40 he disses Aubrey again, as misunderstanding the relationship between senescent cells and aging. Dubious... At 1:17:40 if you look carefully he does the "finger twirl around the ear" gesture in reference to Aubrey, a gesture that is typically associated with someone being crazy, although with his words he says "Aubrey isn't thinking about the pathology [of senescent cells] well."
  • At 1:19:50, he makes an interesting statement. He says that most people (hint - Aubrey) say that damage causes aging. He says that's backwards. Instead, aging permits damage to occur, or "aging causes damage". As we grow older, our telomeres shorten, causing changes in gene expression that results in poorer cellular repair and increased damage. 

Overall, as I said at the top, he comes across more as a salesman, rather than a researcher. He's very optimistic, and it would be great if he's right, and gets a chance to prove it, or be disproven, pretty soon... It seems like targeting AD might be a pretty good strategy to start with. 

 

--Dean

 

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Guest AN

Sorry to post here - will remove it asap once I get a reply. However I could not reply as a guest to most posts. I've been unable to use/log into my account on the CR Society Forum. I'd like to contact an admin to see how to solve this, but have no idea how to contact an admin since as mentioned I can't log into my account. How can I contact an admin to solve? Thank you.

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Hi AN,

 

Send me an email timc [ at ] crsociety.org

 

Include what you remember of your old email account (user name and - if at all possible - associated email address).

 

Also, if you want to setup a new account, we could square that away easily enough.

 

-Tim

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Sorry Tim. I forgot to post here, and apparently AN did as well. I helped her with her login trouble yesterday, via the Facebook group. So we're all good. I'm hoping she'll post to introduce herself shortly!

 

It turns out (for the record) she was trying to use her display name, rather than her login ID to log in. Once we figured that out she was on her way. Rather confusing really... My display name and login ID are the same (Dean Pomerleau), so I wasn't even aware of the distinction.

 

--Dean

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From the below paper I surmise that telomerase is anything but the biggest game in town.

 

 

Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.
Glei DA, Goldman N, Risques RA, Rehkopf DH, Dow WH, Rosero-Bixby L, Weinstein M.
PLoS One. 2016 Apr 6;11(4):e0152486. doi: 10.1371/journal.pone.0152486. eCollection 2016.
PMID: 27049651 Free PMC Article
 
Abstract
 
Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival.

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