Researchers led by a team from the Mayo Clinic in Rochester, Minnesota, have identified a new class of drugs called “senolytics” that target and kill aged—senescent—cells in mice. The team also found that a single dose of senolytic drugs led to improvements in the animals’ health and function.
Previous research has shown that genetically modifying mice to remove their senescent cells extended their health span. This study, published online on March 9, 2015, in Aging Cell, and funded in part by the National Institute on Aging at NIH, is the first to pharmacologically imitate the approach in a mouse model of extremely accelerated aging.
Senescent cells have long been implicated in aging. Some rapidly dividing cells reach a point when they can no longer safely replicate; their telomeres become too short to protect the cell’s DNA. At this point, a cell will either destroy itself through a process called apoptosis, become dysfunctional (and potentially cancer-prone), or turn replication off but continues to survive. The cells that turn off are known as senescent. They can perform some functions, but they also release molecules that may increase risk for a variety of diseases, including cancer.
Senescent cells are not dead. In fact, they cannot die (on their own). This characteristic was key for determining a drug target.
The two senolytic drugs tested, dasatinib and quercetin, were effective individually, but more powerful when used together. Days after a single dose, aged mice showed a notable improvement in heart function. Also, a single dose reversed the damaging effects of radiation on a limb, leading to a lasting improvement in exercise capacity. Longer term, periodic use of the drugs delayed a variety of age-related symptoms, including osteoporosis and frailty.
While dasatinib is an FDA-approved cancer drug, and quercetin has been used by humans as an antioxidant supplement, the researchers cautioned that it is far too early to suggest that they be considered as a clinical intervention for aging. More research is needed to determine whether these and other senolytics have similar effects and are safe in animal models before studies regarding any application in humans can be designed and tested.
Reference: Zhu Y, et al. The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs. Aging Cell. 2015 Mar 9. doi: 10.1111/acel.12344 [Epub ahead of print]