Existing Longevity Therapies that are Technically Feasible, but Difficult and Expensive to Obtain

At the present time it is technically possible to benefit from a small range of therapies that we can reasonably expect to at least modestly slow or reverse specific narrow aspects of aging. I'm not talking about the pills and potions of the supplement sellers here, which are worthless, nor the efforts to repackage a few existing drugs as calorie restriction mimetics, as that is little better. If you want to do something about your long-term health and life expectancy that doesn't require any more effort than a trip to the store, then focus on exercise and calorie restriction - nothing else at that same level of easy availability is anywhere near as effective or as proven. What I have in mind here is instead the first gene therapies, stem cell transplants, and glimmerings of SENS-like repair therapies capable of removing some of the metabolic wastes associated with age-related diseases.

In order to actually undergo one of these new therapies, you would have to undertake some combination of the following: (a) spend money at early adopter levels, high in comparison to the cost a customer would pay for a final product years down the line, (b) network for connections to find access to the necessary services and other items, (c) persuade the small number of current developers to depart from their current practice of adhering to regulation and provide you access, (d) break (the unjust and largely horrible) laws related to provision of medical services, (e) travel to a less restrictive jurisdiction as a medical tourist, and (f) accept a fair degree of risk of failure - that even if everything else goes well, and all involved do their jobs, the present implementation of the treatment just doesn't work, or the present understanding of the science and data provides a false and inflated impression of what the treatment can achieve.

A good example of a combination of most of the above is the BioViva CEO's gene therapy from earlier this year: money and networking are the currency of a startup, and the existence of that startup was required to bring together all the necessary players to get the job done. That and medical tourism to a country where provision of the treatment is legal, as it would be everywhere in a just world. Sadly, in our world, there are entire branches of government in the wealthier nations staffed by those who, day in and day out, toil to block access to potential therapies for people who can make the educated decision to take the risk. This is one of many reasons why medical progress is inordinately slow and expensive. Early adoption plays an important part in the process of development for any technology, and medicine is no different.

Here are a few pointers based on the work of recent years, in no particular order, and with no attempt to be comprehensive. There are others I could list, many of which would fall under the heading of gene therapies in some implementations.

Gene therapies:

With the advent of CRISPR, the technical feasibility of gene therapy is now leaps and bounds ahead of where it was just a few years ago. The remaining challenge in delivery is obtaining reliable tissue coverage in adults; the results in terms of proportion of cells affected is very variable in animal studies, and understanding why these variations occur is an ongoing process. So you can undergo gene therapy and come out with too low a percentage of altered cells to make any meaningful difference.

That to one side, there are any number of gene therapies that are now technically feasible in humans. They span the spectrum of risk. In the most favorable camp are alterations already undertaken in animals for years, that researchers are practiced in, and which appear to be wholly beneficial, such as myostatin gene therapy to spur muscle growth and resist age-related muscle loss. In the least favorable camp there are alterations that could absolutely be set up quickly with CRISPR and a small lab, but have only been carried out in rodents a few times, and with limited long-term observation, such as adding extra lysosomal receptors to maintain youthful measures of liver function in old age via increased cellular garbage collection.

Stem cell therapies:

If you are 60 years old in the US, with a typical level of wealth for that age group, and a typical level of creakiness in the joints, then why wouldn't you spend $10-20,000 on first generation stem cell therapies that have a good expectation value in terms of delivering relief from pain, control of inflammation, improved function, and so forth? The only reason people aren't doing this in droves is that it is still something that you have to know about, to pester the right doctors, to do some legwork on clinics and hospitals. For these very simple treatments you don't even have to leave the country anymore, since the FDA finally relented a few years back, but if you want to save money then heading to Canada or Mexico is very feasible.

If you are younger and your joints are not at that point of constantly reminding you of their damage, the cost-benefit analysis is much less clear. Will a healthy person in their 30s or 40s gain any meaningful benefit - short term or long term - from today's simple stem cell therapies? "No" seems like a very plausible answer to that question, there will be no useful data to help pin down the bounds of the possible for decades yet, and by that time it'll probably be irrelevant.

Enhancing native stem cell activities:

Parabiosis research is uncovering signals in the blood that govern stem cell activities, such as GDF-11. Augmenting or reducing levels of these signals so as to spur greater stem cell repair and maintenance of tissues can be achieved via gene therapies of various sorts, as well as by targeted drugs. This is all still new enough that getting access to treatments would be a case of persuading one or more of a small circle of respected researchers to do this for you, and that just isn't going to happen outside of the context of licensing their intellectual property and funding their development process - things that look a lot like starting a company and building a technology. The risk here is also an unknown; will this spur cancer, or cause other interesting problems? There is too little work in rodents to even be certain of the present safety for laboratory animals.

Thymus restoration:

The loss of much of the thymus in early adulthood slows the supply of new immune cells to a trickle. Expanding that supply would be one way to reverse some of the age-related decline of the immune system. It is possible to grow thymic tissue from cells and transplant it, for example: both things have been done for humans, just not together in one patient. That is a very plausible near-term goal for a clinic outside the US that already has experience in cell therapies or tissue engineering. It is also possible to conduct gene therapy for FOXN1 to restore thymic activity - one of the many riskier options that CRISPR now makes possible should anyone be willing to do it for you.

Immune cell infusions:

Researchers and many clinics are perfectly capable of generating immune cells to order, and in large numbers. It just isn't present practice to make a therapy out of this by delivering those immune cells to patients. It would be a matter of money and organization rather than new science to put together such a treatment given a clinic with the ability to carry out existing stem cell therapies. Provided regularly, such a therapy may well augment the aging immune system with large numbers of new immune cells capable of defending against pathogens and eliminating unwanted cells.

Clearance of transthyretin amyloid:

Earlier this year, promising trial results were announced for clearance of transthyretin amyloid, a form of metabolic waste associated with mortality in the oldest of old people, as well as with heart disease in younger old people. The therapy is one of the first successful implementations of a SENS approach to aging, meaning repair of damage and clearance of wastes, but since it is being developed within the regulatory system it is being used to treat a specific age-related disease rather than as a therapy for a general form of damage that underpins many aspects of age-related degeneration.

This is another great example of a treatment that is technically feasible, has a reasonable expectation to produce some level of long-term benefits to everyone, but the only way to obtain access for the foreseeable future is to have the funds and connections to start a development collaboration with the small group of researchers involved: they are not going to step beyond the bounds of the system. The picture changes somewhat when this becomes a generally available clinical therapy, at which point things come back to medical tourism, but that is still years away for this particular approach to amyloid clearance given the slow pace of regulatory processes in medicine.


Bisphosophonates were shown to grant a sizable five year increase in life expectancy in a study population of a little more than a hundred osteoarthritis patients. Obtaining and using drugs of this nature without a prescription - which you won't get unless you have osteoarthritis or one of the other conditions that bisphosophonates are used to treat - is of course going to be illegal in highly regulated nations like the US. The primary risk is that the data is incorrect, however; an effect of this size should not just appear out of the blue for a class of medicine that has been used for a long time. While researchers are investigating potential mechanisms that might explain these results, this seems a case of data that needs replication and confirmation rather than unquestioning acceptance.


"With the advent of CRISPR, the technical feasibility of gene therapy is now leaps and bounds ahead of where is was just a few years ago. The remaining challenge in delivery is obtaining reliable tissue coverage in adults; the results in terms of proportion of cells affected is very variable in animal studies, and understanding why these variations occur is an ongoing process."

There is quite a bit of commercial investment in developing better viral vectors. I recently read an article where an AAV vector was used to transfect all the muscle cells in a dog model of DMD with a micro-gene-cassette:


Of course I'd really be interested in someone experimenting on a dog with any future nuclear expression of mtDNA sequences that are developed. AAV vectors are probably too small to carry that much genetic material however.

Posted by: Jim at December 28th, 2015 9:07 PM

Thymus restoration is currently being tested in humans in an FDA approved trial run by Greg Fahy. I know some people in the trial and they appear to be doing well, we will know more once the data is in of course.

Posted by: Steve H at December 30th, 2015 6:36 AM

The Wagers lab showed the Thymus can be rejuvenated using stem cells too, I think that is a far more practical proposition personally. The MMTP would like to test that in rats further down the line as we have a stem cell expert in our ranks.

Posted by: Steve H at December 30th, 2015 6:37 AM

Thanks for posting this, Reason. It's a very useful article. It seems lists like this will always be needed. Even decades in the future when tested therapies are seeing widespread usage there will always be another set of therapies on the horizon and people will need to do the cost/benefit analysis about whether to be early adopters.

I've always thought one thing that may benefit those of us really committed to LE and separate us from the public would be practicality. I, and probably most on this board, would be willing to do undergo interventions that would be too bothersome or impractical to members of the general public. Ex: Something that required daily visits to a hospital or lab.

Posted by: KC at December 30th, 2015 1:35 PM

Thanks for this, Reason. This is the first I had heard of an anti-aging affect of bisphosphonates. I took one for years for osteoporosis but was finally switched to another medication that is supposed to rebuild bone rather than just slow down bone loss. I wonder if I am the unwitting recipient of a life-extending therapy. Can you give me the reference for this study?

Posted by: Allen Taylor at January 3rd, 2016 4:33 PM

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