Old cells that refuse to die may lead to treatments for age-related diseases

Research into cellular senescence has taken off in recent years, due to findings that show that clearing these cells from various parts of the body can reverse certain aspects of aging and disease processes. Pharmaceutical industries have taken note, as well, of research that could lead to the development of drugs that might target senescent cells in specific organs or tissues.

In basic research conducted on human cell cultures and on mice, Dr. Krizhanovsky and his team asked, "what, exactly, ties senescent cells to aging?" Are they, for example, a primary cause of age-related disease, or a side effect? And why don't these cells die, despite being damaged, making the "clean-up crews" of the immune system clear them away?

The researchers hypothesized that the answer to the second question might lie in a family of cellular proteins that regulate a type of cell suicide known as apoptosis. They identified two proteins in this family that prevent apoptosis and which were overproduced in the senescent cells. When they injected mice that had an extra supply of senescent cells with molecules that inhibit these two proteins, the cells underwent apoptosis and were then eliminated, and there were signs of improvement in the tissue.

"In small amounts, these cells can prevent tumors from growing, help wounds clot, and start the healing process," says Dr. Krizhanovsky. "But as they amass, they trigger inflammation and even cancer."

Certain common age-related diseases have been shown to be associated with this buildup of senescent cells -- for example, chronic obstructive pulmonary disease (COPD) -- and Dr. Krizhanovsky is hoping to apply these findings to research into treatments for such diseases. The trick, he says, will be to target the offensive cells without causing undue side effects. He has been developing mouse models of COPD and asking whether clearing senescent cells from just the lungs can prevent or ease the disease. Yeda Research and Development, Co., Ltd., the Weizmann Institute's technology transfer arm, is working with Dr. Krizhanovsky to patent and license his discoveries.