Cellular senescence is the concept that normal human cells are ‘mortal’. After a number of divisions, healthy cells can no longer replicate, but remain metabolically active and begin to do things that are detrimental to the functioning of the tissue, organs and the body.
Senolytics are the group of drugs that can eliminate these ‘zombie cells’ from the body. This is expected to reverse physical dysfunction and increase life expectancy, targeting the cause of age-related diseases rather than individual symptoms.
This year, the result of first-in-human studies have been published, indicating that these drugs are a reality that will probably come to fruition sooner rather than later.
The common enemy
In fact, most people seem to either get an assortment of age-related diseases or none. Implying that there is one root cause catalysing them all, suspected to be, at least in part, senescent cells.
Targeting this cause would seem like the logical plan, but although the existence of senescent cells has been known since the sixties, the discovery of senolytics was not made until 2018 by the Mayo Clinic.
The clinic’s study, published in Nature Medicine, demonstrated the anti-ageing qualities of dasatinib, used to treat leukaemia, and quercetin, an antioxidant in several foods. These drugs target the pathways that allow the ‘zombie cells’ to avoid death, killing and clearing them to prevent further harm to healthy cells.
"We can say with certainty that senescent cells can cause health problems in young mice, including causing physical dysfunction and lowering survival rates, and that the use of senolytics can significantly improve both health span and life span in much older naturally aged animals," says James Kirkland, a Mayo Clinic geriatrics researcher who heads Mayo Clinic's Kogod Center on Aging and senior author of the study.
Progressing fast
Less than a year later, first-in-human trials have been conducted and preliminary results published. The Mayo Clinic researchers have continued to be at the forefront, working with collaborators from Wake Forest School of Medicine and The University of Texas Health Sciences Center at San Antonio.
The group have published findings from a safety and feasibility clinical trial for removing senescent cells from a small group of patients with pulmonary fibrosis.
Each participant received the two drugs, dasatinib and quercetin (DQ), taken orally for three consecutive days each week for three consecutive weeks.
The result improved the distance the patients were able to walk with only mild to moderate side effects. This is a huge accomplishment as no other drug has been seen to halt the disease, let alone improve it.
In other findings by the Mayo Clinic since senolytics discovery last year, the drug has reduced memory loss, alleviate the cause of diabetes and reduce anxiety in mice. All depending on the targeted location.
In the Telegraph, Dr Tamara Tchkonia, who worked on the study, enthused: “As an optimistic person I can say we might have these drugs in maybe two years.”
This optimism should be tempered slightly, as blind placebo-controlled studies are yet to be performed. However, barring any major setbacks, these drugs are likely to enter development in the next decade.
