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Dean Pomerleau posted a topic in General Health and LongevityNickola 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
Here is a new 20min video interview of Aubrey de Grey on Youtube in which he covers some interesting topics, including: The self-experimentation Liz Parrish from Bioviva has done to modify expression of genes telomerase & for preventing sarcopenia. Aubrey says there some evidence these modifications could be beneficial. But both have their potential downsides as well (e.g. cancer for telomerase). He admires Parrish for her boldness, and for bringing the possibility of genetic manipulation in humans for health / longevity to the public debate. But he worries that it will be very difficult to identify any measureable benefits that might result from these interventions, since Parrish is young and healthy The newly FDA-approved study of metaformin as a potential anti-aging drug. He is skeptical of CR mimetics like metaformin, due to his skepticism that CR will have much longevity benefit in long-lived species. He applauds the effort to study aging as a disease that can be treated, as this study attempts. CRISPR-cas9 gene editing technology He sees lots of potential for this technology to facilitate the kind of health / longevity interventions his SENS Foundation is investigating He doesn't see a lot of benefits/advantages (yet) for using the other recently publicized DNA technology, DNA_Origami, for drug delivery relative to other drug delivery methods. --Dean