What are senolytics? Drugs, activator, supplements, risks

As we age a higher proportion of our cells end up in a senescent state, which has sparked interest in senolytic drugs and a broader area called senolytics research.

The goal of today’s post is to give you an overview of this important area. How much data are there on efficacy or safety? Is the basic idea here for a possible treatment even valid?

It’s a fun topic so let’s dive in.

senolytics, senolytic drugs
A cartoon imaging an aged, future me in thirty or more years receiving a senolytic drug after which there’s not much left of me. The point is that such drugs will have risks and removing potentially billions of senescent cells, even if such drugs were highly specific, could cause major problems.

Definition of senolytics

Senolytics literally means to lyse (kill and hence pop open) senescent cells.

What do I mean by a senescent cell?

As we age, more of our cells become unhealthy but don’t die. New research has suggested that our old, dysfunctional cells aren’t just sitting there. They can actively harm our health by secreting toxic factors that then negatively impact other cells, tissues, and maybe the body as a whole.

The idea behind the word “senolytics” is to get rid of the senescent or dysfunctional cells. In turn, we could be healthier and we might age more slowly.

When I think about senolytics I remember a joke someone told me as a kid about a woman who had a rusted old pickup truck. Her friend gave her a bottle of rust remover. “Your truck will be like new once you pour that stuff on it and get rid of the rust”, her friend said. However, when she removed the rust, the only thing left of her truck were the tires and a few random parts all in a pile. In other words, the truck was mostly rust and that was holding it together. Inspired by this old joke, I drew the cartoon (above) of myself in the future getting a “rust remover” senolytic drug.

The results could be unpredictable.

The point is that if senolytics remove senescent cells from old people who have very large numbers of such cells things could go wrong.

Senolytic drugs, activator, and supplements

Let’s assuming we want to pursue this idea. Then how would we kill the senescent cells? What would be the cellular “rust remover”?

One notion is that scientists can identify drugs that specifically kill the old cells. Importantly, such senolytic drugs would not target healthy cells.

A recent paper had a list of the most prominent possible senolytic drugs:

Dasatinib, Quercetin, Fisetin, 17-DMAG, Navitoclax, Catechins.

This list fits with the top senolytic drugs that I found in other articles.

Such drugs may work in part by essentially telling senescent cells to kill themselves. This is also called apoptosis.

What are the risks?

Since no drugs are perfect, even a drug highly toxic to senescent cells would likely kill some healthy cells too. The hope is to minimize that risk.

Another risk is that the drugs may tell too many non-senescent cells to die leading to serious tissue damage.

There’s already another level of risk here in an indirect way.

Some folks are trying to capitalize on the senolytic buzz and sell unproven stuff. For instance, I’m already seeing claims that certain supplements can kill senescent cells. There’s no proof of that in my view. One supplement called Senolytic Activator by Life Extension makes such claims. Its formula consists of black tea theaflavins, quercetin, fisetin and apigenin. The marketing goal is to “help manage senescent cell burden and promote systemic rejuvenation”. Where are the data?

What about rigorous senolytics research on specific drugs?

Senolytics data and clinical trials

It is still early days for the senolytics field.

In a Clinicaltrials.gov search I found 19 trial senolytic clinical trial listings. Not all of them are traditional clinical trials. At least one sponsor is a stem cell clinic too, The Steadman Clinic.

However, many of these trials are interventional studies. The target conditions are diverse but include Alzheimer’s disease. Since these clinical studies are largely ongoing, there aren’t much data in people so far.

I did find one published pilot study. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, eBioMedicine. 

This paper generated some buzz. However, in my view, the study showed no clear benefit. Keep in mind it was small and not really designed to produce concrete efficacy results. One serious adverse event was reported as well. I’m not so clear on the safety profile of the intervention there so far. The treatment was dasatinib plus quercetin or (DQ).

The future

Looking ahead, I do think that there is some promise here conceptually.

It needs to be proven for specific drugs and particular conditions in people though. There has been a huge amount of hype about senolytic drugs. Moving forward we can hope that people avoid the hype.

Hopefully we’ll also see sponsors generating high-quality data from well-designed studies to determine solidly if particular drugs or combinations actually have benefits and acceptable safety profiles.

References

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