An Example of Senolytic Self-Experimentation with FOXO4-DRI

Senolytic drug candidates, those demonstrated to selectively remove senescent cells to some degree in animal studies, are fairly easy to obtain. They are not enormously expensive, considered in the grand scheme of things, even those that are not yet mass-manufactured. Removal of senescent cells is a form of rejuvenation, shown to extend life in mice and reverse a number of specific measures of aging and age-related disease. These cells cause harm through the signals they generate, generating inflammation, fibrosis, and many other harmful secondary effects. Given the potential benefits, people are starting to experiment, though so far without the sort of rigor that it would be useful to see. You really have to be measuring appropriate metrics, otherwise it is all too easy to generate no useful information about the effects.

In the example noted here, I'm pleased that someone is making the effort to self-experiment in a public way - something I'd like to see more of, as this is how more organized efforts get underway. He is using the drug candidate FOXO4-DRI recently shown to interfere in the FOXO4-p53 signaling that only takes place in senescent cells. However, he isn't picking useful endpoints to measure, I think, which means that the only evidence gathered here is that this isn't horribly dangerous - always assuming that the supplier is providing what they say they are, which should be checked for compounds that are not presently mass-manufactured and widely used. Bad batches are possible, even with the best of intentions.

Useful or possibly useful items to measure might include the Osiris Green DNA methylation biomarker, bloodwork focused on markers of inflammation, kidney function, and liver function, and CT scans focused on assessing calcification of arteries. If you are not in much later life, however, the changes might be small enough to be hard to detect reliably in easily available tests such as those above, or swamped by normal day to day variation, even if the treatment is useful. Thus the best measure is to take a biopsy and have it stained using the standard research assay for senescent cell presence, but that is custom lab work and harder to arrange for most people.

A senolytic (from the words "senescence" and "lytic" - destroying) is among the class of senotherapeutics, and refers to small molecules that can selectively induce death of senescent cells. Senescence is a potent tumor suppressive mechanism. It however drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Senescent cells accumulate in aging bodies and accelerate the aging process. Eliminating senescent cells increases the amount of time that mice are free of disease. The goal of those working to develop senolytic agents is to delay, prevent, alleviate, or reverse age-related diseases. Targeting premalignant senescent cells could also be a preventive and therapeutic strategy against late-life cancer given the deteriorated efficacy of the senescence response in stopping cancer.

Senolytics are arguably the best rejuvenation therapy currently available, and though costly, FOXO4-DRI is the most effective senolytic. This site is a repository for the first human experiences with this exciting new substance. And, though anecdotal, the hope is this information will prove valuable to early adopters and science. I'm a lifelong experimenter, a member of AAAS, and proud supporter of SENS. I'm hoping the risks I'm taking will benefit many people, and advance the science. I know, I know, this is not a controlled, double-blind experiment. I am patient zero in an n=1 study. But, is there something that can be learned here? Yes, especially if I have a serious reaction or die. Alternatively, if a remarkable rejuvenation becomes evident credibility will be lent to this therapy.