Lecturer Kouhei Shimizu and Professor Fuminori Tokunaga of OMU and Dr. Hiroyuki Inuzuka of Harvard Medical School outlined the molecular mechanisms of various types of cell death and the changes in their regulatory factors that occur with age.

Since senescent cells often have resistance to apoptosis, the best characterized programmed cell death, the removal of this resistance has been a major goal of senescent cell removal therapy. On the other hand, it is not yet known how the relatively new types of inflammatory programmed cell death, such as necroptosis, pyroptosis, and ferroptosis, the molecular mechanisms of which have been rapidly elucidated in recent years, are regulated in senescent cells.

There are also many questions about whether therapies such as senescent cell removal therapy and senomorphics — drugs that only target the harmful senescence-associated secretory phenotype without killing the senescent cells — can be applied to these new types of programmed cell death, and there is little understanding of these either.

“In the last decade, the emerging field of cell death research has developed dramatically, but the relationship with cellular senescence is still undefined,” Dr. Shimizu stated. “Various types of cell death are thought to have great potential as targets for the prevention and treatment of cancer and age-related diseases. We hope this review will accelerate the elucidation of cell death that is effective against senescent cells and the development of methods to inhibit the secretion of harmful substances.”

The findings were published in Seminars in Cancer Biology.