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Tam Hunt: A Conversation with 'Forever Man' Bill Faloon About Fending Off Aging

Noozhawk

11-09-18

Bill Faloon is a man with a mission: to fend off aging. As long as possible, and maybe even forever.

A recent Popular Science story called him "the forever man." This is both because Faloon wants to figure out how we can live forever and because he has been working to resolve this problem for what can seem like forever - or at least since the 1970s, which seems to most of us to be pretty much forever.

Faloon started the Life Extension Foundation in the 1970s, Life Extension Magazine in 1980 and since has served in many roles, always with a focus on longevity and health. His newest venture is the Society for Age Reversal, a public purpose corporation that is, predictably, focused on how to not just slow down or stop but to reverse human aging.

I met Faloon at this year's RAADfest conference in San Diego, where he was omnipresent. When he wasn't on stage giving a talk or appearing on a panel, he was mingling with attendees answering questions and generally offering wisdom where he could. He talks a mile a minute with a soft intensity and keen intelligence.

His mission has gained in intensity because he's not getting younger, and the RAADfest attendees aren't either. He's now 63, and he feels that he and his friends are running out of time. The good news is that there are credible options either here now or soon to be here that may slow and even reverse aging.

One of Faloon's best contributions at the conference was a booklet that summarizes, from Faloon's and the Society for Age Reversal's perspective, the best current science on how to slow down aging. It includes citations so you can follow up on the science yourself if you're so inclined.

The below interview goes into these steps in more detail. Here's the quick summary, in sequence - these assume that you first adopt beneficial lifestyle changes such as good diet, regular exercise, good sleep and good social relations:

Aauthor note: Take these therapies at your own risk and consult your doctor first since most of these haven't been tested yet in human clinical trials or approved by the Food & Drug Administration.

» Metformin, intermittent fasting and/or calorie restriction to boost AMPK and inhibit mTOR, to reduce cancer risk and other aging issues

» NAD+ restoration treatments that include IV infusions, skin patches and supplementation with nicotinamide riboside (NR), to encourage healthy metabolism and energy production

» Dasatinib and quercetin (DnQ) to clear senescent ("zombie") cells, which are one of the key ways in which we age and eventually die

» Young plasma or umbilical cord stem cell infusions, providing new young cells to replace aging or cleared cells after the above steps

» Gene therapy (using CRISPR and other tools) for more specific interventions when this becomes available in the next few years

Faloon doesn't promise that these treatments will keep you healthy or young forever, and he fully acknowledges that the science is steadily changing and improving - as well as the lack of clinical trials yet on most of these therapies. But he does suggest that this step-by-step sequence is the best lifespan and healthspan improvement regime available now, with a lot of good peer-reviewed science to back up these recommendations.

I interviewed Faloon by email in October.

Tam Hunt: Starting off light, you have a great head of dark hair. Are there medications available or coming soon that will actually reverse gray hair throughout the body?

Bill Faloon: We may be seeing some of this with some self-experimentation therapies people are trying such as GDF11 and stem cell exosomes. This is more anecdotal as it is not one of the clinical measures or biomarkers we meticulously test for. Animal studies reveal restoration of youthful coat color in response to some of the therapies that people are self-experimenting with today, including senolytics that remove senescent cells. These broken senescent cells are quite toxic to our aging bodies.

TH: Wyvern Pharmaceuticals (Brad Thompson) made a splash at this year's RAADfest with an announcement about a planned clinical trial to start in 2019 for whole body skin rejuvenation using gene therapies. Do you see this technique as promising for true rejuvenation? Will whole body skin rejuvenation not only give us young and supple skin again but also get rid of gray hair (sorry, I'm starting to gray so this is a personal interest ...).

BF: I have not studied this enough to make an accurate comment. I focus now on seven or eight different approaches to biological age reversal. I expect improvements in skin texture and appearance may be a side benefit, but we are not evaluating this in our baseline and follow-up testing. Other groups are looking at before and after photographs to see if young plasma and other interventions results in people looking younger, in addition to improvements in their clinical measures (like blood pressure dropping) and aging biomarkers (such as reversal of immune senescence).

TH: You provided every attendee of this year's RAADfest, at your own expense, an accessible and useful booklet describing what we can do now to prevent aging and prepare ourselves for real therapies that can turn back the clock, rather than only prevent aging. You don't, however, discuss diet, exercise, sleep, etc., which most consider the baseline things we can focus on to age more slowly and maintain health. Are these things simply assumed in your recommendations and do you agree that these lifestyle options are the foundation for good health?

BF: I absolutely presume that RAADfest attendees are well versed about healthy diet, exercise and sleep, and are also taking an AMPK activator like metformin, bioidentical hormone replacement and proper nutritional supplementation. I never tell well-informed people what they already know. My presentations brought out new information about ways to intervene into aging. Most attendees at RAADfest have been longtime readers of Life Extension Magazine, and as such are thoroughly educated on the basics. What I introduced at RAADfest goes far beyond what we've known for the past 30 years or so.

TH: You recommend the following steps, in sequence, for maintaining longevity under therapies available today: 1. Rapamycin plus metformin for mTOR inhibition; 2. NAD+ restoration with infusions or using precursors like nicotinamide riboside (NR); 3. dasatinib and quercetin to remove senescent cells; 4. young plasma or cord blood therapy. Can you describe how you came up with these recommendations? How confident are you that these therapies won't have negative side effects when done individually or together?

BF: Most people eat too much and this causes mTOR to be chronically elevated, which may preclude optimal results using the other interventions. Rapamycin directly suppresses mTOR. So we believe that inducing autophagy (removal of accumulated cellular waste), which happens when mTOR is suppressed, is a logical first step. What we are finding, however, is that most of our supporters already take metformin, practice intermittent fasting, and/or ingest nutrients that boost a cellular enzyme called AMPK, which indirectly suppresses mTOR. So we feel they may be able to skip rapamycin at first and proceed to boosting their NAD+ as I next describe. We will know more about the additive benefits of rapamycin when a clinical trial we are helping fund wraps up in a few months.

Once cellular health is restored by removal of accumulated debris (via activation of AMPK and suppression of excess mTOR), then the DNA repair effects of NAD+ may be more pronounced. By reenergizing cells using metformin and other AMPK activators to remove waste and suppress fat storage/excess cell proliferation and then NAD+ to repair broken DNA, the body may be more primed for senolytic therapy using dasatinib and quercetin.

Removal of accumulated senescent cells is critical for systemic rejuvenation. Senescent cells secrete protein-degrading enzymes and generate chronic inflammation, both of which can neutralize the beneficial effects of stem cell replacement and/or young plasma that contain a myriad of rejuvenating proteins like GDF11.

What we found, however, is that most RAADfest attendees are already suppressing mTOR using AMPK-activating drugs like metformin, or engaged in intermittent fasting or extreme calorie restriction. So we're now suggesting most of our group take steps to boost their NAD+ levels as Step One (if they are already taking metforming and other AMPK activators) and then proceed to senolytics as Step Two.

If one were to excessively suppress mTOR, this could result in loss of muscle mass and increased frailty. So some people are aggressively boosting AMPK/suppressing-mTOR for three months and then taking a one-month break to turn back up their mTOR for its tissue-rebuilding benefits. We also advise that cancer patients undergoing radiation or chemotherapy designed to destroy DNA in tumor cells avoid boosting NAD+ until they are in a complete response, as evidenced by a PET/CT scan and blood biomarkers of malignant cell activity.

TH: Looking more closely at senolytics, you and many other commentators are excited about the results in model animals and early human results, particularly for the dasatinib and quercetin combo approach, which you describe as being much more affordable now than was the case before. Not all observers agree, however, with Michael Fossel telling me in a recent interview: "The senolytic approach is to remove those ten percent of the cells that are causing damage, and that sounds good, and, initially, it would be. The problem is that the remaining 90 percent have to divide to make up for the missing cells, which means that you've just accelerated senescence in the remaining cells. So, next year, you have to kill another 10 percent, and every time you do that, you're increasing the rate of senescence of the remaining percentage of cells. If you look at graphs of the published data you find that, initially, there's a little improvement in function, and then the vector goes down at a much steeper rate than when you don't do anything at all. That's what I think you're going to find clinically." Does Fossel have a point here or do you think he's being too pessimistic? Can stem cells fill in the gaps (literally) and replace the killed off zombie cells?

BF: Results from a meticulously conducted study at the Mayo Clinic, published in August, showed that aggressive senolytic therapy increased post-treatment survival in lab animals by 36 percent, with their physical functionality also improving. These findings are consistent with other studies in which aggressive removal of senescent cells systemically reverses aging in lab animals. Human data reveal relief of pain and improvement in joint function in response to the senolytic therapy dasatinib and quercetin. We previously had concerns about senolytics like those expressed by respected scientists like Michael Fossel, but the problems he conjectures have not yet manifested and our intention is to replace lost senescent cells with fresh stem cells or young plasma and other interventions. This will revitalize our existing pool of stem cells to replace the functional cells. That should fill any gaps created by senolytics (after repeated treatments).

TH: Can you flesh out your suggestion that we'll be able to use stem cells or young plasma to replace cells lost to senolytics? How will that work specifically?

BF: Infusion of umbilical cord or other sources of stem cells are expected to graft throughout the body, which will at least temporarily replace cells lost to normal aging (via apoptosis) and senescent cells that lose healthy functionality. I say temporarily, because it seems that some stem cell therapies only last six to eight months and then more infusions are needed. We have reason to believe that if our multi-step protocol involving, removing senescent cells (with senolytics), restoring NAD+, and boosting AMPK (which suppresses excess mTOR), the stem cell therapies will have a more robust and sustaining effect. Young plasma contains rejuvenating factors (like GDF11, hormones and other factors) that will help regenerate existing stem cells in our aging bodies.

TH: If senolytics are used many times over the course of one's life at what point will we need the complementary therapies you suggest, like stem cells, to replace senescent cells that are removed with senolytics?

BF: No one knows this yet, but we have comprehensive strategies to deal with this potential eventuality, such as identifying affordable sources of effective stem cell replacements. And please understand that we are not removing that many senescent cells. I've seen microscopic photos of senescent cells in tissues and there are not that many of them. What the Mayo Clinic scientists discovered and published in August (Nature Medicine, reference provided above) is that one senescent cell among 7,000 to 15,000 healthy cells initiate pathologic changes characteristic of degenerative aging. If you look at these photos, there are not a lot of senescent cells to remove.

TH: Do you see these stem cell therapies becoming affordable in the next few years? Or is this an example of a non-exponential technology (and thus following a much slower declining-cost curve than would be the case for a true exponential technology) because they rely on actual stem cells, rather than data, and these biological resources are finite and highly-regulated, at least for now?

BF: It will be very affordable because stem cells can be replicated in large laboratory vats. The question we are investigating now is the quality of excessively replicated stem cells. The good news is that many scientists are working on various techniques to mitigate the replicative senescence that can occur as stem cells rapidly divide in laboratory vats. As with any new technology (like penicillin), it is a bit costly now but will plummet in price as large volumes of healthy young stem cells are mass produced.

TH: You don't include telomerase therapy as one of your steps yet. Bill Andrews, Michael Fossel (again), Liz Parrish, Maria Blasco and many other researchers see great promise for telomerase therapy to lengthen telomeres and restore cell function to a youthful state. Do you agree with these sentiments or is it too soon to say since there have been very limited clinical trials on telomerase therapy at this point?

BF: I agree with the potential benefits of telomere elongation. The problem is we don't yet know how to do it. We do know that healthy behavior patterns slow the rate of telomere shortening.

TH: What about the AAV (adeno-associated virus) delivery vehicles championed by many in the field? Once we gain reliable methods for telomerase delivery where would telomerase therapy fall in your list of top actions for reversing aging?

BF: I know there are a lot of techniques being explored to boost telomerase, which should elongate aging telomeres. I am leaving this research up to others as I advocate for interventions that are available to aging people today, like senolytic therapy and AMPK activation.

TH: What is your preferred umbrella theory for aging?

BF: They all have a good scientific basis. For the first time, we can envision the suppression of excess mTOR inducing beneficial cellular autophagy, which enables us to combat a mechanism of aging that Aubrey de Grey (SENS) refers to as "cellular junk." And the removal of senescent cells should help control what up to now has been treatment refractory inflammation in aging persons.

TH: What's your best projection for when therapies that truly turn back the clock, biologically, will become available? And what's your thinking on the likely costs of such therapies?

BF: As I stated during my RAADfest talks, I believe we are partially there already with the multi-step approach I outlined. I've personally been on even more aggressive experimental therapies since 2012, including using high dose granulocyte colony stimulating factor (GCSF) to increase the release of my own stem cells from their hematopoietic niche and hopefully promote the development of new stem cells. I believe this has improved my cognitive function, but I have no measurements to validate it. I just know I am writing at a rate I did many decades ago and the brain fog cleared after GCSF therapy, which was done over the course of several years. I've observed this effect in others and we have case reports of reversals of neurodegenerative illnesses like Parkinson's in response to GCSF therapy. The NAD+ infusions produced an immediate effect that resulted in marked improvement in my sleep and reduction in blood pressure. These are surrogate indicators of biological age reversal. Since I have no chronic inflammatory pain, I cannot tell if the dasatinib/quercetin (senolytic) therapy yielded outward benefits.

TH: How does GCSF work and how much does it cost?

BF: GCSF is a natural protein that promotes the bone marrow production/release of immune and stem cells. It is used on cancer chemotherapy patients to save them from infections caused by the bone marrow suppression inflicted by most chemo drugs. GCSF costs tens of thousands of dollars to properly administer and it is not one of the age reversal therapies we currently recommend because of its high cost and dearth of large scale research/clinical data.

TH: What other therapies or lifestyle changes do you personally use?

BF: On most days, I intermittently fast for 12 to 18 hours. This provides an opportunity for my bone marrow to rest and be able to produce more hematopoietic cells. I've taken metformin since around year 2000, testosterone replacement since 1997, and consume about 100 different nutrients in concentrated dietary supplement forms to delay pathologic aging mechanisms. I also self-inject 160 mg of NAD+ several times a week to maintain my NAD+ levels at youthful ranges.

TH: What do you use personally for testosterone replacement, and what do you recommend more generally for other men?

BF: Men should have their blood tested for total testosterone, free testosterone, estradiol and PSA. Based on these results, they should go to an anti-aging doctor and have topical testosterone cream prescribed if their testosterone levels are low. If their estradiol levels are high, then they should be prescribed 0.5 mg of an aromatase inhibitor drug (such as anastrozole) twice a week to prevent their testosterone from excessively converting to estrogen, which can be very dangerous. If PSA is elevated, they should defer testosterone replacement until prostate cancer is ruled out. Life Extension Buyers Club (LifeExtension.com) offers these blood tests direct to the public, or they can be done through one's doctor.

TH: You made a big announcement at RAADfest that dasatinib, an important senolytic when combined with quercetin, which has historically been very expensive, is now available at a far lower cost (about $200 for a year's dose as opposed to $2,000 or so). Where can people buy this medication at these costs now?

BF: Several compounding pharmacies are working on this now and we expect to list several of them on the website of our public benefic group called Society for Age Reversal. Interested people can register on this website and not only find low cost sources of medications, but physicians around the country who will prescribe them. The website is RescueElders.org.

TH: How optimistic are you, on a scale of 1 to 10, that we'll have medications that will turn the biological clock backwards commercially available within the next five to 10 years?

BF: Based on what is transpiring now, there should be multiple commercial entities offering these age reversal interventions, which should bring down the cost considerably. For instance, some people are currently paying around $1,400 for NAD+ infusions, but once these are administered in infusion centers with lots of people getting them at once, the price should drop to under $500 per session. (Most people over age 50 have three infusions done over a one-week period and then maintain their NAD+ levels with a precursor vitamin like nicotinamide riboside.)

TH: Last, you've been in this game for a long time - since the 1970s. You've seen a lot of ideas come and go and a lot of optimism grow and then fade. Do you think we're now riding a wave of justified optimism about relatively near-term therapies that will actually turn back the clock and allow us to reach longevity escape velocity in our lifetimes? What are the key differences now?

BF: The ideas of the past involved delayed aging and partial rejuvenation with hormone replacement and other modest approaches. As I opened my talk at RAADfest, a study published in 2018 of a national sampling of Americans reveals a delayed rate of biological aging of around four years, from 1988 to 2010. People who follow healthier lifestyles delay aging even more. So what we've advocated since the 1970s has turned into clinical reality.

Until 2014, however, we never had the scientific validation to recommend approaches to reverse multiple pathologic aging mechanisms. There are now opportunities to intervene and combat specific biological processes that cause us to degenerate and die. And by the way, reporters in the 1970s and 1980s asked us if our approaches to disease prevention and age delay were a "fad." We made it clear back then that better health and longevity is not a fad, and the way that educated people take care of themselves today is a testament to our predictions made decades ago.

- Tam Hunt is a lawyer and writer, and creator of the new Forever Young? blog on all things related to anti-aging.

Articles featured in Life Extension Daily News are derived from a variety of news sources and are provided as a service by Life Extension. These articles, while of potential interest to readers of Life Extension Daily News, do not necessarily represent the opinions nor constitute the advice of Life Extension.

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