Fight Aging!

There are a good many affordable interventions that may well produce enough of an effect on aging to justify widespread use. At the more compelling end of the spectrum, based on a relatively large effect size in animal data and very limited supporting human data, we might consider the senolytic combination of dasatinib and quercetin, stem cell and exosome therapies, and fecal microbiota transplantation from a young donor to an old recipient. Somewhere in the middle lies rapamycin and some bisphosphonate therapies for osteoporosis. At the less compelling end of the list, based on an expectation of smaller positive outcomes and very mixed data for any effect on aging, we find widely used interventions such as hyperbaric oxygen therapy.

But we don't know with reasonable certainty for any of these interventions that it is in fact useful in the matter of aging, as that reasonable certainty requires at least a few fairly large clinical trials, summing to a patient population of high hundreds to low thousands at minimum. Interventions that only slow aging would also require those trials to last a long time, at least five years, in order to generate a meaning signal from incidence of age-related death and disease.

The challenge faced by all affordable interventions, capable of being readily implemented by most clinics, is that no-one has much of a motivation to fund a clinical program that would provide confidence in their ability to slow or reverse aging in specific ways. Regulators in the wealthier parts of the world, in collaboration with large pharmaceutical companies, have made the process of running a responsible clinical trial so very expensive that only a small fraction of the space of all possible therapies can possibly make enough of a profit to justify the investment. Anything that is hard to patent, and thereby obtain some degree of monopoly on the market, is not interesting to investors. Outside of the pharmaceutical and biotech industries, there is only limited funding for clinical trials from other sources, such as academia.

So we have the situation in which therapies potentially applicable to aging can exist in the market for decades without any sufficiently rigorous attempt being made to determine (a) whether they can treat aging, and (b) how good they are at treating aging. What can be done about this?

A variety of initiatives have been underway for some time, to some degree. Some groups want to reduce the cost of medical regulation. Thirty years of very aggressive lobbying, patient advocacy, and activism on this front have yielded just about nothing. Less than nothing, really, as the cost of putting a drug through the FDA regulatory system has more than doubled in recent decades, and the pace at which new drugs are approved keeps falling. It remains to be seen as to whether the present green shoots in the US regulatory system, such as Right to Try laws, will make any difference, but so far rhetoric from inside the system about accelerated approvals and reducing costs remains rhetoric.

A subset of those interested in reducing the cost of regulation are specifically engaged with the question of how to make clinical trials cost less. This is a complicated topic, and little progress has been made for many of the same reasons that regulation is expensive in the first place. Those in charge have little short term incentive to reduce the costs of the system; bureaucrats use it to diffuse blame for failures, while large pharmaceutical companies use the high cost of development as a moat to defend against upstart competitors. Everyone involves recognizes the flaws in the system, and no-one does anything about it because it is not in their immediate interest to do so.

Some groups devote themselves to making therapies available outside the major regulatory systems, via medical tourism. This has been relatively successful in the provision of therapies, albeit to a comparatively small number of people relative to those that could be reached if treatments were available in heavily regulated regions, but it has absolutely failed to generate an environment in which hard, reliable data on the efficacy of such therapies results. The medical tourism field is a black box; one roughly knows what therapies are available, but that is about it. Everything else is hidden, unavailable. First generation stem cell therapies have been widely used for more than 20 years, and we still know relatively little about efficacy in most use cases.

Some groups are trying to build systems and communities for self-experimentation and medical tourism participants that are specifically designed to yield higher quality data that might form the basis for synthetic clinical trials. So far this has not generated any meaningful success. It is a hard problem. All of the incentives are for patients and clinics not to share, and if one is paying enough to change those incentives, one is back to effectively running a less well organized form of expensive clinical trial.

Overall the problem of proving that an affordable therapy is or is not worthwhile as a treatment for degenerative aging is a challenging mess. For my part, I suspect that producing good data on low-cost interventions is going to require, at least at the outset, for the first dozen or so interventions, a community of dedicated, wealthy philanthropists who care more about this topic than they do about being wealthy. To my eyes, philanthropic support of clinical trials is the only short-term practical approach to bring change that might demolish the present set of perverse incentives, or at least lead to a few of the most interesting of the affordable potential interventions for aging being proven and quantified in clinical trials.