An Example of the Beneficial Role of Senescence in Injury

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.



Most senolytic drugs mess with the cell matabolism to force apoptosys on cells in distress by impairing the signalling or repair mechanisms. When we have a body in distress it is normal to expect worse results if you srat messing with those mechanisms. What is interesting, however if the senolitycs were given just a day before the injury would there be deterioration (do we need to have resident/standby population of ScS ? ) and to what degree. Also another question is can senolytics help with better repair if given after the initial wound healing has started. Say given after 1,2,10 days of the wound.

My guess is that we still need some number of ScS in standby for the first part. The second part is probably very tissue and wound specific. In some cases it could greatly reduce scarring if the SASP can be muted down. Probably during wound healing it is better to use senomorphs that reduce inflammation but don't kill the senescent cells.
I guess my questions will require several studies to answer :)

Posted by: cuberat at October 8th, 2020 7:50 AM


btw, you are doing a great job at finding and annotating all those articles. It looks like a product of a full-time job or even a team.

Posted by: cuberat at October 8th, 2020 7:53 AM

Might simply mean that for a few days after senescent cell treatment you stay home and take it easy to minimise risk of accidental injury.

Posted by: Link at October 9th, 2020 4:35 AM

Life extension, whose supplements are always top rated, has a weekly senolytic treatment. This theory makes a weekly treatment seem unwise. I can see where keeping them from building up with weekly treatment sounds good but after reading this not so sure.

Posted by: august33 at November 13th, 2020 3:19 AM
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