How soon is forever?

An update on the prospects for near-term life extension therapies

“What’s in your stack?”

“What?” I responded.

“Your supplement stack, what’s in it?”

I understood now. He was asking what supplements I was taking, with “stack” indicating that he assumed I was taking enough supplements to comprise a stack. Disappointingly, I’m only taking two supplements right now, I told him, so not really a stack at all.

He then showed me his pages of notes on the stacks he takes each day. Here’s a sample:

A RAADFest 2018 attendee’s notes on his daily supplement “stack.”

We were at the 2018 Revolution Against Aging and Death Festival, which everyone just calls RAADFest, in San Diego, California. This is one of a growing number of conferences focused on the science of longevity and how to slow or even turn back the clock on aging. This is the third RAADFest and it’s an interesting mix of science conference and almost-religious rally and party.

The science presentations didn’t go into the kind of detail you’d expect at a more traditional science conference, but there were a number of interesting talks that included enough science to pique the interest of the more geeky types like myself.

The almost-religious part of the event is a bit tongue in cheek, perhaps best exemplified by the presence of Bill Faloon’s Church of Perpetual Life, an actual church (legally speaking, at least) in Florida that focuses more on the science of aging, and ways to stay put on this plane of existence, than on how to enter the pearly gates of heaven.

Nevertheless, there is a bit of a big church feel to the event, with founders and organizers Jim Strole and Bernadeane (she only goes by her first name) rallying the troops at the main stage during the beginning and end of each day’s set of talks. They did a great job of humanizing the global effort to extend lives and, maybe, even one day turn back the clock on aging. Their comments focused on friendship and life enjoyment, and how the people there at the conference may really be your best friends because they all want you to live forever, they want you to do well in life, and they want the same for themselves.

De Grey finds religion

While some more hard-core science aficionados may dismiss RAADFest for not having a strong science focus, regular attendee and member of the RAADFest steering committee, anti-aging science pioneer Aubrey de Grey, feels that RAADFest is a highly effective and valuable event because of its focus on generating enthusiasm for life itself (yes, some “Debbie downers” don’t always view life as a gift) and for increased longevity to enjoy more of what our lives can offer.

De Grey often has to battle with critics of the anti-aging movement in terms of questions about the impacts on the planet from much longer lives, the social and societal impacts, and more generally why would anyone even want to live forever? These are all important questions, of course, but most thinkers who have examined these questions in depth have concluded that longer and healthier lives will likely be a boon not only for the individuals enjoying longer lives but also for the planet and humanity in general.

De Grey wrote about this year’s RAADFest:

[M]ore and more academics are seeing that they will not tarnish their reputations among their future peer reviewers by speaking at an event such as RAADfest. Indeed, the same applies beyond academia: one of this year’s other keynotes was Jim Mellon, a billionaire whose reputation in the world of finance is immense, and who has become the most prominent (and high-rolling) early-stage investor in the nascent rejuvenation biotechnology industry. … Congratulations, Jim [Strole] et al: you have created a major new string to the bow of the longevity crusade.

I met many of the biogerontology luminaries at the conference, including De Grey and Reason (yes, he goes by just his first name), CEO and founder of Repair Biotechnologies, as well as the founder of the well-known blog FightAging!. When I first spoke with him at the conference he came across as a bit of a pessimist about near-term (next 5–10 year) longevity treatments. But in his own review of the conference he seemed more optimistic, stating(hyperlinks in original):

I spent an interesting few days last week attending RAADfest, and came away somewhat optimistic that this strange collision of subcultures may herald an acceleration in the adoption of solid science and working therapies on the part of the anti-aging marketplace, accompanied by a driving out of the ineffective nonsense and fraud of past decades. This sea change is very much a work in process, and there is plenty of that nonsense still to be found. Yet the advent of senolytic therapies to clear senescent cells has clearly invigorated certain groups, who have now turned a sizable amount of their advocacy and attention to the adoption of this first legitimate rejuvenation therapy, an implementation of the SENS model of damage repair.

Respected British billionaire investor Jim Mellon gave a talk on the main stage and made a great point: the current global market for anti-aging products is about $140 billion — but nothing actually works in terms of extending life spans! He predicts, quite reasonably, that once we have a product or two that actually does something measurable (as judged with clinical trial results) for lifespan we’ll see a global gold rush into what he calls “juvenescence” (anti-aging) companies.

This “will be the biggest stock market mania” in history and juvenescence will “be the biggest industry on the planet.” Jim and his partner Al Chalabi wrote a 2017 book about all of this, which I’ve read and highly recommend, called Juvenescence: Investing in the Age of Longevity. As the title suggests, the book is about the science of longevity and how to invest in this rapidly-growing field.

He also talked about various promising treatments available now, including metformin and vitamin B12, rapamycin, NAD+ restoration (nicotinamide riboside and other similar NAD+ precursors), and the senolytic combo of dasatinib and quercetin (more on these below).

At RAADFest, Mellon made some bold predictions: that average life expectancy will be 115 years by 2050 (up from today’s roughly 80 years); that gene therapy will extend that to 150 years; and that many significant new developments will happen in the next few years alone.

He wrote his first book on biotech in 2012 and a number of world-changing events happened in just the few years between his 2012 book and his 2017 book, including: CRISPR gene therapy; major AI advances; an HIV cure; and development of effective immunotherapy for various cancers. So it’s not hard to imagine that the next 5–10 years will bring unexpected and equally important changes.

Liz Parrish, also on the RAADFest steering committee, spoke about upcoming additions to the BioViva Sciences (the company she founded) platform, including developing better biomarkers to assess the effects of various anti-aging treatments (they just hired a whole new team of bioinformatics specialists); developing better adeno-associated virus (AAV) delivery vectors for getting gene therapies into cells where they belong; and remote personalized longevity counseling.

Parrish also spoke about the latest results of her personal experiment with telomerase therapy (which has been global news for some time now), reporting that her telomeres continue to lengthen and are now measured at 8.12 kilobase-pairs, up from 7.33 in 2016 and 6.71 in 2015 before she first took the experimental treatment. At about 5 kbp, cells generally cease to function and eventually die.

She said that her telomere length is now comparable to a 30-year-old even though she is 47. She also told me that software analysis of her face concluded that she looks like she is 25.

We spoke briefly and if I hadn’t known who she is I’d have thought she was an attractive and in- great-shape 35-year-old, not my contemporary at 47.

I asked her when she thought telomerase therapy might become affordable for most people and she told me that it “will become affordable to practically all in the mid 2030s.” I’m hoping it’s a lot sooner than that, but time will tell.

Brad Thompson of Wyvern Pharmaceuticals, in a quirky and slightly awkward talk, excited me and the rest of the audience by announcing that his company will be starting human clinical trials on a potentially ground-breaking whole-body skin rejuvenation treatment in 2019. He said that the treatment is based on already-established treatments that Wyvern and other companies that he owns or is part of have developed. He had high confidence that the treatments will work. He predicted that if all goes well we’ll have commercially available whole-body skin rejuvenation therapies available in about three years. That seems highly optimistic, but as with Parrish’s more pessimistic forecast, time will tell.

Thompson also told the audience that he personally expects to live long enough to live forever.

Ray Kurzweil, who popularized this phrase along with many other longevity ideas and terms, such as “longevity escape velocity,” was a keynote speaker. His talk was disappointing to those who expected new ideas because it was mostly a rehash of his decade-old framework for anti-aging: Bridge 1 (good nutrition, exercise, supplements, etc.); Bridge 2 (coming biotech improvements that may actually turn back the clock); Bridge 3 (nanotech that may be able to sustain our youth in perpetuity); and Bridge 4 (eventual transcendence of biological form with uploading of consciousness into the cloud).

He did introduce his latest book, Danielle: Chronicles of a Superheroine, a novel targeted at young girls to inspire them to go into STEM fields as a career.

But long-time Kurzweil fans like me expected more from the great man.

The promise of telomerase therapy

Bill Andrews, another elder of the field, spoke about his latest research in telomerase therapy. His company, Sierra Sciences, has an agreement with Libella Therapeutics to license his technology for the world’s first human clinical trials with AAV-delivered telomerase. Libella is setting up treatment labs in Colombia, Vanuatu and Singapore and plans to offer whole-body telomerase treatments like that received by Liz Parrish in 2015. Parrish’s treatments cost more than $100,000 but it’s anticipated that the treatments will be a lot cheaper when these treatments become widely available.

Michael Fossel (not at RAADFest this year) discussed his projection that by 2025 or so we should have approximately $100 IV telomerase treatments that can turn back the clock. He acknowledged in an interview with me, published here, that this is not any kind of firm prediction but more of a challenge to the industry. Again, time will tell.

I asked De Grey at the conference what his views are on telomerase therapy now since he’s proposed a polar opposite approach that he calls Whole-body Interdiction for Lengthening of Telomeres (WILT). His proposal, fleshed out in his 2010 seminal book, Ending Aging, suggested that an effective way to cure cancer would be to eliminate the body’s ability to produce telomerase, thus preventing cancer cells from replicating past the Hayflick limit of 50 or so cell divisions. The downside of WILT, of course, is that it would also eliminate the body’s ability to use telomerase to lengthen telomeres in non-cancerous cells. De Grey thinks this price might still be worthwhile because all of the rest of his SENS (Strategies for Engineered Negligible Senescence) program should be able to maintain good health and longevity even without longer telomeres.

De Grey clarified in our conversation that he actually agrees with Bill Andrews and other telomerase therapy advocates on about 95 percent of all anti-aging science, and that he proposed WILT more as a way to air contrary views to prompt responses from colleagues. He seems to acknowledge now that it may be more promising to focus on using telomerase to lengthen telomeres rather than eliminating telomerase.

Parrish, Fossel and Andrews, perhaps the best-known telomerase therapy advocates, have been touting Spanish researcher Maria Blasco’s promising results (Muñoz-Lorente, et al. 2018, finding “no detectable cancer-prone effects in the context of oncogene-induced mouse tumors.”) finding that telomerase therapy has not increased cancer risk in lab mice. It’s still too early to weigh in with much certainty about the actual promise of telomerase therapy in humans, but with a number of clinical trials expected in the next few years it shouldn’t be long before we have more definitive answers.

What can we do today?

Bill Faloon, another elder in the field but still looking and sounding spry at 63, spoke a number of times and also offered all attendees a succinct booklet summarizing his organization’s recommendations on available treatments for extending life. His main recommendations are as follows, in order: 1) rapamycin to inhibit mTOR, which improves heart health and lowers cancer risk; 2) NAD+ restoration with IV infusions, patches or pills (in that order in terms of effectiveness) to improve metabolism and DNA repair; 3) the senolytics dasatinib and quercetin to clear away senescent cells. He also spoke highly of the potential for young plasma and stem cells to replace cleared cells eventually.

His top three recommendations were echoed by Jim Mellon and various other researchers and commentators, but there are no human clinical trials yet on most of these, or on their combination, so try these approaches at your own risk. There is a long and outstanding debate over the merits and safety of self-experimentation and Reason has a great piece here describing protocols that should be followed.

Are effective anti-aging therapies on the horizon?

Now, back to the stack questions. What’s in my stack? As mentioned, not much currently. But after the conference, various interviews, and after quite a bit of additional research, I’ll be adding a few things to my personal stack. More to come in a later piece as to what specific supplements, etc., I’ve decided to add.

One of my questions going in to this conference was whether optimism is warranted about relatively near-term effective aging interventions. We’ve had decades (centuries?), of course, of debate about these issues and how soon we can expect reasonable to slow or even halt aging. There seems to be a growing consensus that we can reasonably expect at least some effective treatments in the coming decade, maybe two.

Kurzweil reiterated his view that Longevity Escape Velocity will arrive by the late 2020s. Under this approach, even if the first round of effective treatments “only” add a decade or two to our lives, we can then expect that that decade will bring new discoveries and new treatments that will extend our lives another twenty years or so. Then rinse and repeat and Kurzweil’s view is that we are at that point effectively immortal.

I won’t venture a guess at this juncture about the actual timing of LEV or effective treatments. But there is certainly a growing body of research and active or pending clinical trials that will soon yield better answers.

Stay tuned for separate interviews with many of the people mentioned in this conference report.