Quercetin Is a Natural Senolytic Found in Onions, Kale, and Apples

In 1936, Albert Szent-Györgyi, who won the Nobel Prize for discovering vitamin C, suggested that a class of phytonutrients called flavonols should also be considered a vitamin. The most common flavonol in the diet is called quercetin, which is found concentrated in onions, kale, and apples (It’s what gives apple peels their bitter taste.). Researchers had been testing dozens of different compounds on cells scraped from umbilical cords and then irradiated to force senescence. In 2015, they announced their results: quercetin was a natural senolytic.

Quercetin was combined with a senolytic drug called dasatinib and shown to alleviate the disability of young mice injected with senolytic cells, as well as extend the lifespan of naturally aged older mice. Even starting the senolytic cocktail late in life (the human equivalent of 75 to 90 years-old) resulted in a 36 percent longer average lifespan. When the same combination was found to start clearing senescent cells within 48 hours in freshly excised human tissue (fat taken during abdominal surgery), researchers decided to try putting it to the test in people.

Idiopathic pulmonary fibrosis is a relentlessly advancing and invariably fatal disease of lung scarring linked to cellular senescence. The average survival after diagnosis is less than three years. So, 14 pulmonary fibrosis sufferers were given a combination of quercetin and dasatinib a few days a week for just three weeks and experienced significant and clinically meaningful improvements in physical function—the distance walked in six minutes, the time to walk four meters, and the time to stand up and sit down from a chair five times. Now, there was no control group to control for placebo effects, and the performance metrics are subject to learning—that is, people tend to do better the more times a task is performed, just given familiarity. Nevertheless, it’s certainly a promising start. Randomized double-blind placebo-controlled trials are underway.

We still didn’t have proof senolytics could eliminate senescent cells in whole humans until 2019. Blood and tissues samples were taken before, and 11 days after, three days of quercetin and dasatinib therapy in study subjects with diabetic kidney disease. The tissue burden of senescent cells and blood levels of key SASP factors both dropped, directly demonstrating senescent-cell clearance. It seems to take weeks for new senescent cells to develop, which is presumably why they were able to demonstrate benefits even more than a week after the quercetin and dasatinib cleared from their system. This suggests senolytics could be given in a “hit-and-run” manner, once every few weeks. This is good, because drugs like dasatinib are toxic.

In less than a month, most people taking dasatinib suffer bone marrow toxicity and risk a slew of other side effects. What about just taking quercetin alone? Mice made fat and sick with high-fat diets suffer kidney tissue senescence and dysfunction that can be reversed with quercetin, but the dose used was massive—the equivalent of eating on the order of 20 pounds (9 kg) of onions. Remarkably, though, quercetin doses as low as the human equivalent of one small apple a week significantly reduced cellular senescence and improved the healthspan of aging mice. For example, they experienced less hair loss, enhanced heart function, and greater athletic endurance into the equivalent of their sixties. OK, so you may want to share a few kale stems with your pet mouse, but what about in people? That’s exactly what I’ll address, next.