Young anti-aging field takes big step with Mayo Clinic senolytics showcase
The idea that flushing senescent cells — those old, fatigued cells that cease to divide — from the body may rid the body of harmful proteins has been one of the prominent proposals in the anti-aging sphere. Having generated a stream of animal data to support the hypothesis, the Mayo Clinic now has results from an early human study suggesting they have found drugs that can do exactly that.
To be sure, the main goal of the Phase I trial wasn’t to show the effects of decreasing senescent cells in the body; rather, the scientists were keen to prove that a senolytic regimen they’ve tested in mice works the same way in humans.
This is significant because despite the publication of first-in-human data in January, “so far, there has been no direct demonstration of senescent cell clearance by senolytic drugs in peer-reviewed published human clinical trials,” the authors wrote in EBioMedicine.
For the small trial, researchers deployed dasatinib and quercetin; the former is a cancer drug also known as Sprycel while the latter is a plant derivative. Nine patients with diabetes-related chronic kidney disease were recruited and given the treatments for three days.
While the drugs were out of the system within a few days, the effects appeared to persist, the team — with LaTonya Hickson and Larissa Langhi Prata as the co-first authors — reported:
Key markers of senescent cell burden were decreased in adipose tissue and skin biopsied from subjects 11 days after completing the 3-day course of D + Q, as were key circulating SASP factors, compared to before administration of these senolytic drugs.
Such proof about the mechanism of action bolsters their previous work suggesting that a brief course of dasatinib plus quercetin improved physical functions for patients with idiopathic pulmonary fibrosis — a tough-to-treat disease.
While small-scale, the trial is a significant step forward for the translation of senolytic therapies, according to Ronald Kohanski, deputy director of the division of aging biology at the National Institute of Aging.
“The demonstration that senescent cell numbers can be reduced in two tissues in humans is an important advance based on the compelling evidence from studies in laboratory mice,” he said in a statement.
Chronic kidney disease is just one of many age-related ailments that the team believes senolytics can delay, prevent or treat, said senior author James Kirkland (who heads Mayo’s Robert and Arlene Kogod Center on Aging).
His colleagues at Mayo have previously flagged Alzheimer’s and Parkinson’s as diseases where purging senescent cells can make a big difference.
In case anyone gets overly excited, though, the scientists felt the need to conclude their paper with a note of caution:
The field of senolytics is new. The first clinical trial of senolytic agents was only reported in January 2019. The findings reported here are preliminary results from an ongoing clinical trial of senolytics for treating dysfunction in patients with diabetic chronic kidney disease. Fewer than 150 subjects have been treated with these drugs in the context of clinical trials that we are aware of so far. In addition to side effects related to individual senolytic drugs known from other contexts in which those drugs have been used, there could turn out to be serious side-effects of senolytics as a class, which are not yet known. We caution against the use of senolytic agents outside the context of clinical trials until more is known about their effects and side effects.