Fight Aging!

I think that in years to come, we'll consider 2015 to be the point at which things really started to move for SENS rejuvenation research. It has to be said that medical research moves slowly at the best of times. It takes a good long run-up to show results, and it took a decade for SENS to grow from an idea and a few interested researchers to its present state of a foundation, the support of leaders in the research community, a loose network of research groups, and a few newly formed startup companies. It is perhaps an appropriate year for the unveiling of the Methuselah 300 monument, listing the donors who provided the initial funds and support to start this ball rolling.

Senescent cell clearance as a treatment for degenerative is having its breakout year. The Methuselah Foundation and SENS Research Foundation provided seed funding to Oisin Biotechnology for work in mice on a method of clearing senescent cells. Meanwhile another research group spent 2015 uncovering tissue specific drug candidates that tip senescent cells into the mode of programmed cell death called apoptosis, demonstrating this in mice with a couple of different drugs, producing results good enough to prove that meaningful health benefits result from a single treatment in older animals. This work should once and for all settle that SENS advocates have been right for the last decade, and the rest of the research community should have listened years ago.

It has also been a breakout year for gene therapy, but in a much bigger way. CRISPR has reached critical mass, and we are going to see an avalanche of gene therapies taking place in the years ahead both in trials and outside the regulatory system. A demonstration of this point was made by the BioViva CEO, who used medical tourism and the connections of a biotech startup company to undergo telomerase and follistatin gene therapies. Five years from now, it won't take any connections - just look up a reputable clinic outside the US and take a trip. If you look back at the progression of stem cell therapies since the turn of the century, that is exactly what is going to happen for the first gene therapies. Very few of the plausible candidates are what I'd call rejuvenation therapies at this point, more compensatory approaches that can spur additional stem cell activity or muscle growth or the like, but the growth in expertise in gene therapy in the field as a whole is a good thing for the future of SENS treatments that do require gene therapy.

Glucosepane cross-links are an important contribution to aging in humans - they are a part of the reason that skin and blood vessels lose their elasticity. The former is unfortunate, the latter ultimately fatal. For some years now the SENS Research Foundation has been funding efforts to develop the tools needed to work with glucosepane in cells and tissues, and this year a first success was published in a prestigious journal: a reliable method of synthesizing glucosepane as needed, a very important part of the toolkit.

Another lengthy SENS research program now blossoming is the use of allotopic expression of mitochondrial genes. The researchers originally funded by the Methuselah Foundation and SENS Research Foundation formed a company, Gensight, that is now well on its way to clinical application of this technology for inherited mitochondrial disease. That foundation of practice and experience will hopefully create a much better basis to finish up the work for all mitochondrial genes and the treatment of aging in the years ahead.

The long-running efforts by SENS researchers to find bacterial enzymes capable of breaking down some of the waste chemicals that form lipofuscin, a mix of metabolic wastes that clogs up lysosomes in old cells, have reached the point of commercial development. Candidate drugs have been licensed out to newly formed Human Rejuvenation Technologies, Inc.. Now we wait and see how that goes, but in general you should consider these sorts of deals a way to bring in more money for later stage research - it's just less visible until it reaches its goals.

Even the cancer programs based on preventing the lengthening of telomeres at the SENS Research Foundation are getting more attention from publications, and are no longer alone in the research community. Other groups are striking out in their own attempts to suppress cancer by preventing cells from lengthening their telomeres.

Speaking of commercial development: this year's Rejuvenation Biotechnology conference was a success. The hand off from academia to industry doesn't just magically happen in any field, and longevity science is no exception to this rule. This conference series exists to build the relationships and awareness needed for a smooth transition of rejuvenation therapies from the laboratory to biotech startups and Big Pharma in the years ahead.

Amyloid clearance inside the Alzheimer's research community continues to be a long, slow, painful progress of advancement by small degrees. This is not the only sort of amyloid, however, and this year efforts to clear transthyretin amyloid - associated with heart disease in the old and heart failure in the very oldest individuals - met with success in a human trial. This is perhaps the most advanced of SENS repair therapies at this point in time, an actual honest to goodness narrow scope rejuvenation therapy with a successful trial behind it. Next up should be an sober assessment on how to jailbreak this advance out of the regulatory regime and into more general availability via medical tourism.

2015 saw continued and louder debate within and around the scientific community on the topic of whether or not aging should be officially defined as a disease. I expect this discussion to continue to grow, given the financial and regulatory incentives involved:

• From the 2014 International Conference on Aging and Disease
• Why Seek to Classify Aging as a Disease?
• Another Call to Classify Aging as a Disease
• Insight into the Machinations of Classifying Aging as a Disease
• Aging as the Greatest Disease of All
• Arguing that Public Reluctance to Treat Aging as a Medical Condition is at Root a Categorization Problem

Crowdfunding by the longevity science community continues apace. We're still not as good at fundraising as our nearest cultural neighbors, the strong AI philosophy of development typified by the Machine Intelligence Research Institute, but a little friendly competition never hurt anyone. That branch of the strong AI community, like SENS and much of the radical life extension advocacy community, arose from the transhumanist communities of the past few decades, and many of the same people have interests on both sides of the fence. It seems reasonable to think that we can do just as well as MIRI and related organizations when it comes to pulling in funds for our goals in healthy longevity. This year the Fight Aging! matching fundraising held in collaboration with the SENS Research Foundation raised $250,000 for rejuvenation research, and an earlier crowdfunding project at Lifespan.io raised $45,000. We're improving year over year, but there's much further to go yet.

What about the large investments in our space? Calico continues to make deals and be a mystery to anyone other than the insiders, but increasingly looks like something halfway between Big Pharma and the NIH, which is to say irrelevant to any meaningful progress towards human longevity in the near term. It will be sad if it ends up another Ellison Medical Foundation, but that may well be where things are heading. The principals at Human Longevity Inc. are much more vocal in talking up their position, but are definitely not doing anything that is of great relevance to life extension - it's more a personalized medicine company with great PR, nothing exceptional. You might look at a good interview with Aubrey de Grey and Brian Kennedy from earlier this year for more on these two initiatives. On a different and more positive note, philanthropist Peter Thiel has been talking more openly about his interest in longevity science this year: I think it is important the people who are backing the more important ventures speak out in this way.

Off in the research community interested in slowing aging, the population of people without large amounts of funding in other words, advocacy for change is continuing. A trial of metformin to treat aging is being used to change the way in which the FDA views aging and therapies - at least I hope that's the intended goal here, as I have no expectation that this will move the needle on human health and life span. The Longevity Dividend advocates have, meanwhile, set down their scientific evidence and vision for more NIA funding for therapies to gently slow the aging process in a new book.

Parabiosis research, linking together the circulatory systems of an old and a young individual to identify factors that may influence or be influenced by aging, is proceeding apace. It is being used to identify various potential drug targets, mostly with the expectation of increasing stem cell activity in old individuals. The debate over the validity of previous discoveries, such as GDF-11, also continues.

As usual there have been some novel or early and odd results here and there in the literature, things that stand out and make you wonder. We can never expect anything of relevance to emerge from any of these, but you never know. For one, researchers identified a marker for less fit cells, and by eliminating those cells made flies live longer - with a lot of subtlety in what exactly "less fit" and the presence of the marker actually means. In other news, a company is working on therapies using isotope replacement in water, based on evidence suggesting that this increases resistance to oxidative stress in proteins and slightly slows aging. Elsewhere, the quest to understand the suspiciously large gain in life expectancy resulting from bisphosphonate treatment for osteoarthritis in a study some years ago has progressed to a hunt for plausible mechanisms. I'd rather see an attempt to reproduce the initial results. Elsewhere again, researchers provided evidence to show that twins with different exercise levels do not have any longevity differences - which is hard to reconcile with what the data presently shows on exercise and its benefits.

On a completely different topic, a novel Alzheimer's theory is that accumulation of amyloid is due to a slow physical failure of drainage channels for cerebrospinal fluid near the nose. As a theory this has the attractive property that it is comparatively easy to prove or disprove, and the Methuselah Foundation funded a test this year - so we shall see. In other news, the types of age-related diabetes are multiplying again; the assignment of Alzheimer's disease as type 3 diabetes seems to be an ongoing unresolved debate, while researchers have recently produced a much more compelling set of data in support of a type 4 diabetes caused by a novel form of age-related immune dysfunction.

The cryonics community provided a demonstration of memory retained in vitrified and restored nematode worms, a great piece of evidence to support the hypothesis that present cryonics practices are sufficient to preserve the fine structure of the human brain. Other evidence continues to be presented in the Brain Preservation Foundation technology prize contest, and in a milestone the year James Bedford became the longest surviving human being to evade the final end of information-theoretic death. This year also saw the launch of a new research-focused cryonics collaboration in the UK.

Researchers investigating proficient regeneration in salamanders have uncovered an unsuspected link between harmful senescent cells and this regeneration: salamanders suddenly become very good at clearing senescent cells while they are regrowing a limb. In zebrafish, another regenerative species of interest, researchers used a human gene to turn off limb regeneration, a result that perhaps points out why this desirable feature doesn't exist in our biology. In other news, researchers using decellularization of donor organs as a tissue engineering strategy have advanced to the point of being able to decellularize and repopulate an entire rat limb and all of its structures. Other researchers have restored the immune system in mice with transplants of engineered thymus organoids, grown from cells. In another area of regenerative medicine, a team showed that converting nerve cells into photoreceptors could restore sight to mice with degenerative blindness - a possible alternative to more conventional visions of cell therapy.

Lastly, here are links to a few short commentaries that might be worth reading again, you never know. Certainly I'd forgotten that half of them existed:

• Is it Different this Time Around?
• The Scientific Institution is Biased Against Shortcuts to the Production of Practical Technology
• Disappointing Comments on Longevity Science From Bill Gates
• The Arcane
• The Immortals Among us
• The Relevance of SEC Changes to Crowdfunding Rules
• Existing Longevity Therapies that are Technically Feasible, but Difficult and Expensive to Obtain
• Scores of Labs Should be Gearing Up to Work on Glucosepane Cross-Link Breakers, But Are They?