Any consideration of treating aging as a medical condition should primarily focus on the few true rejuvenation therapies that are now arriving at the point of clinical trials or availability via medical tourism. This became a topic worth keeping an eye on in 2017 with the commencement of the first formal human trials of senolytic therapies - as well as a fair amount of quiet, unofficial self-experimentation. This and other classes of treatment noted here will typically directly address the low-level cell and tissue damage that causes aging, following the SENS vision for rejuvenation through repair. The goal, the point of interest, is to turn back aging by reversing its causes.

Caveat Emptor: Most Potential Therapies for Aging are Marginal at Best

Bear in mind that true rejuvenation therapies, those that are based on repair of the cell and tissue damage that causes aging, and thus capable in principle of producing sizable benefits for old people, are still a minority concern in the field of aging research. Most of the new potential therapies declared by one or another authority to be a means to treat aging are marginal at best. These are pharmacological approaches that tinker with the operation of metabolism to modestly slow markers of aging, and will not be included here. Examples include the TAME metformin trial, as well as tests of rapamycin, nicotinamide riboside, and the like. The results in humans from these therapies seem likely to be smaller and less reliable than those produced through exercise or the practice of calorie restriction - and more to the point, these are only ways to slow aging, not to turn back its causes in order to produce actual rejuvenation.

Senolytics to Clear Senescent Cells

The first accessible human trials for senolytic drug candidates capable of selectively destroying senescent cells are underway. Some of these can be discovered via by searching for suitable terms, such as "senolytic", or the names of relevant drug candidates. Using "senescent cells" as a search term will likely pull in too many unrelated cancer and obesity studies, swamping the useful results. Small pilot trials of senolytic drug candidates have been conducted by the Betterhumans non-profit organization, several research centers including the Mayo Clinic, and biotech companies such as Unity Biotechnology. These are initially focused on individuals 65 and over with specific conditions strongly linked to senescent cells in animal studies, such as osteoarthritis, metabolic syndrome, and fibrotic kidney disease.

The only approach so far robustly confirmed to be senolytic in humans is the combination of dasatinib (a chemotherapeutic) and quercetin (a plant extract supplement). These can be obtained and used, given a physician willing to prescribe off-label for senolytic use.

Regrowing the Thymus

The thymus is a small organ responsible for turning thymocyte cells into T cells of the adaptive immune system. It atrophies with age, and is largely fat in most 50 year olds. The rate at which new T cells are created to reinforce the aging immune system falls as the thymus atrophies, and this is a major component of immune aging. Numerous groups are interested in ways to regrow active thymic tissue, but so far the only type of therapy that is both confirmed to work in human patients and close to clinical availability is the growth hormone based approach pioneered by Intervene Immune. As of 2021, that company is running small clinical trials in older volunteers to bolster their early positive results.

Amyloid Clearance Trials

Amyloids are one of the distinguishing marks of old tissues, are created as a side-effect of the normal operation of metabolism, and so should be removed. Numerous attempts to clear amyloid-╬▓ in patients with Alzheimer's disease have been made, most via immunotherapy. Until very recently, success was elusive. Search to see the scope of this effort. Trials are only open to patients suffering from later stages of Alzheimer's disease, and until the expectation of benefits is improved and the risk inherent in this class of therapy is greatly reduced, this isn't about to blossom into greater availability.

Also worthy of note, while the latest therapies, in 2020 and later, have in fact robustly lowered amyloid levels in the brains of Alzheimer's patients, there was little to no observed benefit to cognitive function or pace of decline. Amyloid aggregation is harmful to tissues, so should be removed as a part of any comprehensive rejuvenation effort, but it appears to be a less important mechanism than hoped in later stage Alzheimer's disease.

Separately, progress has been made in clearance of transthyretin amyloid, associated with heart failure. A few approaches, such as SAP antibodies and CPHPC have shown promise in human trials. These efforts were overtaken by the development of small molecule drugs such as tafamidis, approved in 2019, that interfere in the misfolding of transthyretin amyloid, altering the natural balance of creation and clearance in favor of clearance. Given the existence of an approved drug with a good safety profile, it is in principle possible, given the right connections and approach, to obtain it for off-label use, but it never hurts to wait for more than just a few years of data.

Restoring a More Youthful Gut Microbiome

The gut microbiome changes with age in ways that reduce its benefits and increase chronic inflammation. Fecal microbiota transplantation from a young individual to an old individual has been demonstrated to rejuvenate the gut microbiome, improve health, and lengthen life in animal studies. In humans, the size of the effect is unknown. Fecal microbiota transplantation is in an interesting gray area of regulation; it isn't approved by regulators, but is comparatively widely practiced by clinicians in cases in which the gut is overtaken by pathological bacteria.

Reversing Presbyopia

While not yet approved, the drug initially known as dioptin (and now coded as UNR844 at Novartis) is in early clinical trials. It is a formulation of lipoic acid choline ester that acts to break a form of age-related cross-linking that stiffens the lens of the eye. That stiffening prevents the muscles controlling the eye from achieving focus at near distances, leading to presbyopia. The results are good enough to suggest keeping an eye on this project.

Considering Stem Cell and Exosome Therapies

Do currently available stem cell therapies produce rejuvenation? This can be debated. The most commonly used stem cell therapies, such those involving mesenchymal stem cells that are widely available in clinics and via medical tourism, fairly reliably produce reductions in chronic inflammation for some period of time, but little more than that. More specialized therapies that might be argued to carry out repairs are far less readily available, and there is decidedly mixed evidence for any specific approach to in fact meaningfully and reliably address causes of aging. There is clearly a bright future for this field, but most of the promised gains have yet to materialize.

Meanwhile, it is clear that much of the benefits realized by stem cell therapies are produced by the signaling generated by transplanted cells in the short time before they die. Much of this signaling is carried by extracellular vesicles such as exosomes, which can be harvested and used in therapy more cost-effectively than the cells themselves. While exosome treatments analogous to mesenchymal stem cell transplants are less widely available than those stem cell treatments, they are available.

Last updated: December 16th 2023