While the main goal of the Phase I trail was not to show the effects of reducing senescent cells in the body the researchers were eager to show that the anti-aging senolytics that were tested in animal studies can work the same way in humans as “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, despite the publication of the first human data in January.
Dasatinib and quercetin were given to 9 patients with diabetes related chronic kidney disease for 3 days in this trial. The drugs cleared participants systems in a matter of a few days, but the effects persisted and the 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.”
Proof on the mechanism of action bolsters previous work suggesting a brief period of treatment of the senolytic cocktail improves physical functions for patients with very difficult to treat idiopathic pulmonary fibrosis.
This trial may have been small but it is a significant step towards translation of senolytic therapies. “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,” said Ronald Kohanski, deputy director of the division of aging biology at the National Institute of Aging in a statement.
The team believes that chronic kidney disease is one of many age related ailments that senolytics will be able to delay, prevent, or treat, according to senior author James Kirkland. Purging these zombie cells has also been shown to make a difference in Parkinson’s and Alzheimer’s disease.
However promising the trial was the paper was concluded 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.”
