Preclinical study finds senolytics clear up to 70% of ‘zombie’ cells

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Senolytics—a class of drugs that reduce chronic inflammation and tissue damage in aging cells—are shown to eliminate 30% to 70% of “zombie” cells in the body. These zombie cells, known as senescent cells, stop dividing and don’t die, ultimately contributing to a host of diseases of aging, including cancer.

A preclinical study from Cedars-Sinai, published in Aging Cell, had three key findings:

• Senolytic drugs purge the most harmful cells, leaving less-harmful senescent cells behind.
• These remaining “senolytic-resistant” senescent cells can be activated into tissue-damaging senescent cells by infections and other factors in the environment of senescent cells.
• A new class of drugs, “senosensitizers,” can enable senolytics to eliminate these lurking senolytic-resistant “ticking time bomb” cells.

Investigators found that in laboratory mice treated with senolytic drugs, the remaining senescent cells were less inflammatory and damaging than the cells removed by the treatment. Researchers also found that these remaining senescent cells, when activated into tissue-damaging cells by an inflammatory environment, become more vulnerable to senolytics than those in a stable environment.

Based on their findings that infections can make senescent cells become susceptible to senolytics, study authors theorize that targeting senescent cells with newly developed senosensitizers—and then senolytics—might allow more senescent cells to be removed than when using senolytics alone. This could remove senolytic-resistant senescent cells and reduce the impact of infections in previously apparently healthy older people.

“This drug combination, which is still in the preclinical phase, has the potential to target senescent cancer cells that persist after radiation and chemotherapy and may later reemerge as more aggressive disease,” said James Kirkland, MD, Ph.D., director of the Center for Advanced Gerotherapeutics and senior author of the study.