A major gap exists in the present spectrum of efforts to develop the means to treat aging, rejuvenate the old, and turn back age-related conditions. An the one hand, a small number of promising potential therapies to treat the mechanisms of aging can at present be applied by physicians off-label, or otherwise without the need for a great deal of interaction with the FDA. On the other hand, there are a good hundred or more clinical indications, specific age-related conditions recognized by regulatory authorities, that might be improved by these therapies. Several hundred small, informal trials could be run, starting now, given approaches that presently exist, in order to determine whether or not these forms of therapy are in fact effective.
Let us only consider the senolytic combination of dasatinib and quercetin, for example, a low-cost treatment that can be given off-label and that has been demonstrated to clear senescent cells in human patients. Clearance of senescent cells in mice produces profound and rapid rejuvenation. Senolytics as a class of therapy are at present in human trials for only a few indications: osteoarthritis, idiopathic pulmonary fibrosis, COVID-19, chronic kidney disease, and recently Alzheimer's disease. The whole senolytic industry, and associated academic trial groups, after nearly ten years of development, has done no more than initiate a few formal human trials, at great expense, and which are very slow to answer the question of whether this actually works well. Senescent cells are involved in some way in near every age-related condition, disrupting tissue function throughout the body, provoking chronic inflammation. Effects on the full panoply of age-related conditions could be assessed. This is not being done.
If considering small informal trials, let us say that one aims for 100 to 200 people per trial, more than enough to produce meaningful evidence for efficacy when the effect size is significant. With volunteer efforts, cheap off-label treatments and low-cost assays for suitable endpoints, this sort of informal trial can be conducted for $200,000 - which is exactly what Lifespan.io is doing for their PEARL trial of mTOR inhibition. The model works. Even if the cost were $500,000 or $1,000,000, then that would still be vastly cheaper than the full, formal FDA IND process. A single non-profit with significant funding could run many such trials in a year, generating human evidence at a much greater rate than the scientific community and biotech industry combined are managing at the moment.
That evidence is much needed. There is an enormous amount of funding sitting on the sidelines. Funding that could be supporting the deployment of senolytic drugs to the population, or could be running large-scale formal clinical trials to validate the use of senolytics. The organizations capable of deploying that funding are very conservative. They will only start in on such project after there is already proof, after the debate is already won. Which is why we need the results of many low-cost trials - in order demonstrate that dasatinib and quercetin is a meaningful and useful approach to the treatment of aging.
Everything said above about the dasatinib and quercetin senolytic combination also applies to, say: fecal microbiota transplantation; or periodic blood plasma dilution; or the Khavinson peptides for thymic regrowth; or the Intervene Immune approach to thymic regrowth; or CASIN for CDC42 inhibition and restored immune function; or injection of stem cell derived exosomes; and forth into a growing list of approaches that may well be capable of achieving good results in old people. Many of these are already being used by self-experimenters, but that will never generate the sort of data that is convincing to the powers that be. There is tremendous potential to demonstrate benefits in older individuals via addressing one or more of the underlying mechanisms of aging, and the world is instead largely squandering time as the clock keeps on ticking on all of our lives.