“Avoid the use of DQ as a senolytic therapy”

Forever Healthy Foundation issues risk-benefit analysis on dasatinib + quercetin as a senolytic.

The Forever Healthy Foundation today published its latest risk-benefit analysis, which explores the combined use of cancer drug dasatinib with quercetin, a polyphenol common in plants, as a senolytic therapy.

Based on promising results in animal models, the combination of the two compounds, also known as DQ, is thought to eliminate senescent cells in humans with the accompanying health and rejuvenating benefits.

After screening more than 3300 scientific papers and analysing more than 150 clinical and pre-clinical studies, Forever Healthy concludes that the use of DQ as a senolytic therapy should be avoided – “until there are more published results showing benefits in humans, a clearer picture of the senolytic-use specific risk profile, and a consensus on treatment protocols.”

“You have to look at the risks and benefits, especially for something like senescence.”

Back in September last year, Professor Lynne Cox told us: “You have to look at the risks and benefits, especially for something like senescence. Senescent cells are crucial in early development, so healthy young people and people hoping to have children really should stay away from senolytics. It’s about finding the right tempo to act at: not too slow to miss out but not too fast to overlook key safety regulations.”

Based in Germany, Forever Healthy is a non-profit initiative with the mission to enable people to vastly extend their healthy lifespan. Today’s report is the fifth to emerge from the organisation’s Rejuvenation Now initiative, which identifies potential rejuvenation therapies and systematically evaluates them on their risks and benefits, and publishes the results freely in an online database.

We caught up with Dr Isabelle Schiffer, scientific spokesperson for Forever Healthy, who explained more about the purpose of their knowledge base.

“We realised that there is a lot of knowledge already out there and the first rejuvenation therapies [are] already on the market, you can buy any of the supplements,” she says. “So we wanted to add scientific background so that people or medical doctors are aware of the risks and the benefits of those treatments.”

Since its first report on NAD+ restoration therapy in August 2019, Forever Health has also published rejuvenation-centric analyses on the use of fisetin as a senolytic therapy, low-level light therapy for skin rejuvenation, and the use of EDTA for vascular rejuvenation.

Schiffer points out that these reports are not just for the benefit of scientists and doctors.
“We are basically aiming for everyone, especially the people who are interested in the field, understand the background and are curious about testing these rejuvenation therapies,” she says. “We want to give them advice so that they have enough information about the risks of taking [a therapy], what are the benefits of taking it and the best way to apply it.”

So what led Forever Healthy to focus on DQ in its latest analysis?
“DQ was the first combination to be effectively working against senescent cells and we had the feeling that a lot of people are now wanting to use this,” says Schiffer. “The first clinical trials in-human were done in 2019 and they are now in phase 2, so it’s something that is progressing and we felt like now is a good time to really assess the risk and benefits to inform people who are interested in that field.”

Despite the foundation’s recommendation to avoid the use of DQ as a senolytic therapy, Schiffer is keen to point out that this is only based on current understanding and that it still has “a lot of potential.” She cites a 2018 study in mice led by the Mayo Clinic’s James Kirkland, which showed positive results in terms of health span and lifespan, but notes that there are still relatively few studies out there.

“We really need to define the therapeutic window – when do we start treating patients and humans?” says Schiffer, noting that dasatinib is a cancer treatment that has a lot of side effects. “With all the rejuvenation therapies we are aiming to treat healthy people, so there cannot be a lot of risk associated with that because we want to have a benefit. So yes, at the moment, we see too many risks to provide DQ as a senolytic for healthy people.”

Image courtesy of the Forever Healthy Foundation