Researchers here provide an interesting demonstration of the beneficial role of transient cellular senescence in injury. Applying senolytics to selectively destroy senescent cells immediately following traumatic injury greatly worsens the consequences. Senescent cells are harmful when they build up and linger in tissues over the course of later life. The signaling they generate is useful in the short-term, such as by mobilizing the response to injury in numerous cell populations, but very damaging when sustained for the long term. This dynamic is one of the reasons why we should favor infrequent senolytic therapies that destroy only the harmful, lingering senescent cells, rather than continuing treatments that would negatively impact regeneration and other functions by also destroying transient senescent cells.
It’s called senescence, when stressed cells can no longer divide to make new cells, and it’s considered a factor in aging and in some diseases. Now scientists have some of the first evidence that at a younger age at least, senescent cells show up quickly after a major injury and are protective. Their model is hemorrhagic shock, a significant loss of blood and the essential oxygen and nutrients it delivers that accounts for about 30-40% of trauma-related deaths from things like car accidents and shootings; and their focus the liver, one of the many major organs that can fail in response.
Shortly after hemorrhagic shock occurs, a population of liver cells quickly become senescent. To find out if the rapid movement to senescence they saw for some liver cells was good or bad, researchers gave some of the rats in their studies senolytics, a relatively new class of drugs that target senescent cells for elimination. Laboratory studies of these drugs have shown they can prevent or improve age-related problems like frailty, cataracts, and vascular and heart dysfunction. Early trials in humans have also reported success in reducing the progression of problems like diabetes and kidney related damage.
But when younger rats in hemorrhagic shock were given the drugs as part of the fluids used for resuscitation shortly after blood loss, they all quickly died. When the researchers gave the same senolytics to healthy rats, they were fine. Death of the senescent cells appears to exacerbate the tissue injury resulting from blood loss. Researchers suspect the rapid transition to senescence that occurred in a population of liver cells was an attempt to stabilize after the trauma, and likely transient. While he says you can’t generalize that what happens in one tissue, like the liver, will happen in another organ, the researchers expect something similar happens in other organs in the face of serious injury.