Senescent cells are an important research target as a number of age related and inflammatory diseases are implicated in the accumulation of these cells. With age more cells become senescent and no longer replicate, yet they remain metabolically active. Around the world researchers are investigating possible ways to reverse the process of cellular senescence, while others are investigating how the cells are cleared and why the efficacy of the process wanes with age.
Weizmann researchers initially started out to gain better understandings of how the immune system is involved in removing senescent cells from the body, and they discovered perforin proteins play a key role in immune surveillance, particularly in relation to clearing senescent cells. Mouse models with silenced perforin genes were observed to suffer from an increased accumulation of senescent cells and faster rate of age related diseases.
Administering the perforin diminished animals with ABT-737, which was previously found to enhance clearance of senescent cells in lab and animal experiments, the animals displayed physical and behavioral improvements resembling younger healthy mice. The immune system is suggested to have an important part in clearing senescent cells, and age related decline in the immune system function may be a key part of various age related pathological symptoms in life and healthspan.
Unfortunately ABT-737 is not transferable to be safe for human uses. Originally designed as a cancer treatment to inhibit specific proteins that block cellular death early clinical trials revealed it had a terrible side effect of producing thrombocytopenia. While this treatment may not be the breakthrough awaited for, it does suggest that improving immune system ability to remove senescent cells may be an effective way to restore more youthful functions, as published in the journal Nature Communications.
