Young Inside

During the postdoctoral studies he conducted at Cold Spring Harbor Laboratory in New York before coming to Weizmann, Krizhanovsky and his colleagues revealed that cellular senescence plays a much more active role in fighting and preventing various diseases than previously thought. For example, tumors shrink during chemotherapy not only because cancer cells self-destruct, but also because a rising number of these cells becomes senescent.

Moreover, Krizhanovsky discovered that in the liver, cellular senescence is necessary to prevent disease. When liver cells are damaged by the hepatitis virus, fatty liver disease or alcohol abuse, cells called fibroblasts start dividing to repair the damaged tissue. Krizhanovsky found that when the fibroblasts undergo senescence and stop reproducing, the repair process stops and the tissue can return to the normal, pre-damage state. This senescence is needed to prevent a different kind of damage: It averts fibrosis, the overproduction of scar tissue by the fibroblasts, which in turn can lead to cirrhosis of the liver, a common cause of death in developed countries.  

Krizhanovsky then showed that yet another important phase in the healthy maintenance of tissues is the clearance of such senescent cells from the body. In the liver, the immune system’s “natural killers,” the NK cells, enter the picture, removing the senescent fibroblasts. If the removal is impaired or if the fibroblasts don’t become senescent, the result is continuous liver damage. “Cellular senescence provides first aid, like a clamp fastened on a torn artery to stop bleeding,” Krizhanovsky says. “But just as the clamp will cause harm if it’s not removed in time, so senescent cells that are not cleared properly from the body start releasing inflammatory substances, which in the long run cause damage to surrounding tissues.”