A Gameplan to End Age-Related Disease

SENS, the Strategies for Engineered Negligible Senescence, is the only presently plausible road to the prevention and cure of all age-related disease that could be accomplished in a short enough period of time to save most of those reading this today. It is a repair-based approach to treating the causes of aging, taking the present scientific consensus on the fundamental cellular and molecular differences between old and young tissue, and providing detailed plans to produce treatments capable of reverting or working around all of them. Given funding of a hundred million dollars a year, functional rejuvenation treatments following the SENS proposals could be demonstrated in mice a mere decade from now. The chief problem at this time is that we stand a long way away from that level of funding.

This is not to point out a lack of success: far from it. The existence of the SENS Research Foundation and its present $5 million yearly budget is just one of the visible signs of fifteen years of hard work and advocacy to bring a vision into reality. Fifteen years ago there was no SENS research and the scientific community was largely unwilling to talk about treating aging in public, for fear of endangering their ability to obtain grants. Yet today this is a line of research now widely supported within the scientific community, and researchers are far more willing now to talk about treating aging. Progress towards meaningful rejuvenation treatments is progressing more rapidly today than it ever has. These are still the early years in a longer process of decades, however, and we have barely started to climb the funding mountain, and barely started to build the aging research community of tomorrow.

Large-scale funding for rejuvenation research in the SENS model will happen eventually. No other faction in the research community is proposing or working on anything that can possibly be as effective as repair of damage in aging tissue. So over the course of time SENS will inevitably take over the research community mainstream simply by virtue of the fact that it will produce meaningful results in early stage work while other approaches to treating aging will continue to fail miserably on that count. The pressing question is how long it will take, give that the clock is ticking for all of us. In helping SENS move faster we are quite literally running for our lives.

Here is a recent article on the work of the SENS Research Foundation, and while all publicity is good publicity, I'm forced to note that is somewhat annoying to see the 2005 SENS challenge given so much of a focus, while only passing mention is given to the fact that the SENS Research Foundation is now an organization with scientific programs running in numerous noted laboratories in the US and Europe, as well as a scientific advisory board that includes well-known luminaries in the fields of genetics, tissue engineering, and other fields relevant to aging research. The decade old debate as to whether or not SENS is serious science was had and done and the skeptics lost because they were wrong. End of story, and way past time to move on.

Against the Biological Clock - A Gameplan to End Age-Related Diseases

To Aubrey de Grey, the body is a machine. Just as a restored classic car can celebrate its hundredth birthday in peak condition, in the future, we'll maintain our bodies' cellular components to stave off the diseases of old age and live longer, healthier lives.

Dr. de Grey is cofounder and Chief Science Officer of the SENS Research Foundation and faculty at Singularity University's November Exponential Medicine conference - an event exploring the healthcare impact of technologies like low-cost genomic sequencing, artificial intelligence, synthetic biology, gene therapy, and more. Recently speaking to participants in Singularity University's graduate studies program, de Grey said the greatest challenge in aging research today is less of a technical nature, more a misguided focus in the mainstream.

Most approaches to age-related disease aim to manage symptoms. They have contributed to longer life expectancy and eased complications, but because treatments interfere with the body's finely tuned systems, they can have nasty side effects and are ultimately powerless (even with advances) to reverse age-related illness. Why? "Aging is a side effect of being alive in the first place," says de Grey.

Metabolic processes drive the day-to-day business of living, but they also inevitably cause cellular damage. The body's range of self-repair mechanisms don't take care of everything. Eventually, a lifetime of accumulated damage causes the familiar signs of aging like "thinning skin, cloudy eyes, muscles sapped of strength, heart disease, and cognitive decline." Negligible senescence is a term used to describe certain animals that don't display symptoms of aging. De Grey believes we can use biotechnology to engineer negligible senescence in humans, and he cofounded the SENS Research Foundation to lead the way.

Comments

To be fair to the author of that blog article the 2005 SENS challenge does neatly encapsulate some of the issues around funding SENS. Namely that it is a hypothesis that can only really be tested out by developing the technology. So arguments about whether or not it will work will rage until the day we have a rejuvenated mouse.

The only major difference between now and 2005 is that senescent cells have been demonstrated to have some pretty negative effects in a progeria mouse model.

Posted by: Jim at August 5th, 2014 12:46 AM

I'd like to respond to the opening sentence about SENS. I think it's the most plausible but not the "only presently plausible" approach. Since SENS therapies aren't here now, we have to interpret "presently plausible" in a broad sense of presently plausible to pursue for eventual implementation. Here are a few other approaches that have some plausibility albeit not as much as SENS:

1. "Nanomachines gonna do it" - This is another damage repair approach that aligns with SENS but emphasizes more advanced methods of delivery that can rejuvenate more thoroughly. Proponents may think that the envisioned delivery methods for first-stage SENS therapies are inadequate or that alternatives will arrive sooner than expected. A variant would emphasize synthetic biology, which overlaps with "soft" or biomimetic nanotech.

2. "Farm the bodies" - This approach would emphasize that we already know how to grow young organs, even integrated systems of them! Developmental biology has already accomplished this. The idea would be to grow patient-matched whole bodies without the brain for transplantation purposes of varying sophistication. The main barrier here is even stiffer sociological blow-back than SENS. At least any surplus could always be turned into human burgers...

3. "We robots now" - Would concentrate on developing sophisticated and portable life support systems for the brain; more aesthetic, life-like and functional androids; and brain-computer interfaces.

1 & 3 have their advocates, while 2 is not acceptable in polite company. With 2 there would be an incentive to harvest the bodies as soon as possible which would lead to 100 year-olds who look 10 and other mischievous knock-on effects of such like. Advocates of 3 do a fair job of skirting likely outcomes that would make conservative heads explode. Just consider popular styles of erotic art to get some idea what would come of allowing people to design their own custom "avatars" free of biological constraints on form.

Approaches 2 and 3 need elements of SENS that deal with brain rejuvenation. Since SENS is incremental and envisions the advent of future therapies of increasing sophistication to achieve longevity escape velocity, it can shade into these other possibilities in the long run.

If you want to call B.S. on anything I've said, just don't omit to show how any of this is less plausible than reviving cryonics patients with their brains shattered into 3-d puzzles of labyrinthine glassy chunks, a proposal touted in these parts with apparent seriousness.

Posted by: José at August 5th, 2014 1:09 AM

@ Jim, debate should rage however the technology review debate had very little mention of the actual SENS proposals. The only one mentioned in any detail is WILT. It would be more productive if the critics gave some thought to those specific ideas on age related diseases and whether or not there would or could be some benefit. The challenge was not whether or not SENS leads to an indefinite lifespan but whether it was worthy of discussion. All of the ideas in SENS, particularly removing lipofuscin using bacterial enzymes, is worthy of that.

In spite of that the review is about 10 years old and is starting to look very dated. Submissions supporting the negative side mention science that has been conducted and shown to be of some benefit. If you are a journalist and you mention that article, in spite of the myriad of developments since that time, then you are lazy.

Posted by: Michael-2 at August 5th, 2014 4:54 AM

@José: The critical part of that opening claim was "in a short enough period of time". I guess I should have emphasized that point. You are correct and it is absolutely the case that mature molecular nanotechnology will lead to ways to replace our biology with better, longer-lasting machinery. I just don't see that or other methods turning up on a similar time frame to SENS; they are much harder problems, much earlier in their development.

Posted by: Reason at August 5th, 2014 5:41 AM

@Reason: I read that caveat, but I still disagree with the claim of sole plausibility for SENS. AdG has mentioned several times that he holds out "at least a 10% probability" that SENS therapies will not come to fruition for 100 years. Meanwhile, I don't think the achievement of these other methods can be excluded on circa a 50 year timescale, well within the lifetime of many currently living people.

Progress in A.I. is a big unknown and good progress could change our view of the relative difficulty of different kinds of problems. SENS, for instance, will have a large trial-and-error component; that is, independent trial and error of many different therapies. A.I. probably cannot accelerate this element dramatically. By contrast, for nanomachines much of the difficulty resides in coming up with one sweeping master-stroke of ingenious and meticulous design. That's the kind of problem on which the advanced powers of inference of a strong A.I. could be brought to bear.

Posted by: José at August 6th, 2014 2:15 AM
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