Removing senescent cells extends lifespan up to 35 percent in mice

Scientists used a compound to remove senescent cells from mice, which lengthened the animals’ average lifespan by as much as 35%. Clearing senescent cells in the mice not only gave them a longer life but a healthier one by delaying tumorigenesis and diminishing age-related inflammation in the kidney, heart, and fat, according to the study published online February 3, 2016 in the journal Nature.

If the therapy eventually works in humans as it did in mice, it “may be an attractive approach to extend healthy lifespan,” the authors explained.

Cellular senescence plays a positive role in defending the body against cancer by halting the proliferation of damaged or dysfunctional cells. But the accumulation of senescent cells, and the components they secrete, may also result in age-associated diseases and dysfunctions.

In this study, investigators sought to determine whether eliminating senescent cells removes useful cells along with the detrimental ones. They used a transgenic mouse model that allowed for the drug-induced elimination of senescent cells. When the mice reached middle age (12 months old), the researchers began biweekly administration of a compound called AP20187.

At the end of the study, researchers determined that clearing senescent cells in treated mice extended their median lifespan by 25% to 35%. It also delayed the formation of tumors and reduced age-related deterioration of several organs. In addition, the treated mice showed a healthier appearance and a reduced amount of inflammation in fat, muscle, and kidney tissue, without apparent side effects.

"Senescent cells that accumulate with aging are largely bad, do bad things to your organs and tissues, and therefore shorten your life but also [shorten] the healthy phase of your life,” said the study’s senior author Jan van Deursen, PhD, Chair of Biochemistry and Molecular Biology at the Mayo Clinic, in Rochester, MN.

Because the study findings showed no negative side effects, “drugs or other compounds that can eliminate senescent cells would be useful for therapies against age-related disabilities or diseases or conditions,” Dr. van Deursen added.

The researchers are optimistic about the potential implications of the study for humans. “The advantage of targeting senescent cells is that clearance of just 60% to 70% can have significant therapeutic effects,” said the study’s first author Darren Baker, MS, PhD, Assistant Professor of Biochemistry/Molecular Biology at the Mayo Clinic. “Because senescent cells do not proliferate rapidly, a drug could efficiently and quickly eliminate enough of them to have profound impacts on healthspan and lifespan.”

The researchers further explain the study's findings in thisvideo.