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Senescent may be good after injury


corybroo
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Senescent cells may be good when it comes to a bad injury

at a younger age at least, senescent cells show up quickly after a major injury and are protective.

shortly after hemorrhagic shock occurs, a population of liver cells quickly become senescent.

If the cells switch immediately to a senescent state, they may help prevent organ failure

when younger rats in hemorrhagic shock were given the [senolytic] drugs as part of the fluids used for resuscitation shortly after blood loss, they all quickly died.

Death of the senescent cells appears to exacerbate the tissue injury resulting from blood loss, and the drugs that target those cells also have off-target effects that are problematic with an injury as opposed to age-related senescence

This is the first evidence that cellular senescence can develop within a few hours after tissue injury, that hemorrhagic injury can make that happen and that the senescent cells that emerge are not detrimental in this scenario.

there are parallels between significant injury and aging, particularly the fact that mitochondrial function—energy production by the cell—decreases in both

senescence can be a death sentence for cells, which start to secrete factors called SASPs, which get the attention of the immune system so the cell may be tagged for elimination by immune cells 

But it may also make cells far less vulnerable to programmed cell death, or apoptosis, which cells can initiate when they have irreparable damage

They also found increased levels of the SASPs, or senescence-associated secretory phenotype markers, things like growth factors and enzymes that break down proteins and peptides, secreted at high levels by senescent cells, again much like in the livers of aged rats. SASPs can be good and bad, causing problems like insulin resistance and inflammation, but also aiding wound healing and tissue regeneration.

they found senescence is not bad and may actually be good in the aftermath of injury. In fact, the cells can even heal in this hunkered-down state.

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Thank you, corybroo, this pretty timely, as I'm recovering from a dental implant procedure - the insertion of a titanium screw, which was a pretty intense procedure. I'm on a restricted diet as a result (no hot beverages etc.), and I elected not to eat at all for 48 hours and only drink water (24 prior to the surgery and 24 after). So naturally, I'm curious about recovery from injury (which the surgery is a form of).

Boy, the more one learns, the more complicated it all seems. Particularly the aspect of how the same process can be good or bad depending on the context - sometimes senescence might be good, sometimes bad. This confirms for us the difficulty involved in coming up with interventions, such as the recently much touted senolytics - which may not be good in some contexts.

In general, aging is a response as much as an event. Many processes only occur when we age - but trying to prevent them may be counterproductive, if the reason for their existence is an adaptive process that ameliorates some other insults of aging. That's where simplistic interventions fail - for example, when it was observed that this or that hormone level falls as we age, that may be an adaptive process and trying to bring those hormone levels back to "youthfull" levels may be very destructive. Our bodies respond to aging by ameliorating various aging negative effects. We mess with this at our peril.

This is why it's so important to evaluate everything from an overall outcome perspective. All Cause Mortality - very hard to do in humans given the time scales. Merely looking at the response to some biomarker or another can be very deceptive - perhaps an intervention in the short term appears to bring you back to a youthfull level but at the cost of sharp deterioration longer term, like ingesting meth for "energy" only to crash disastrously later on, for a net negative.

It's sobering how much we don't know and are unlikely to know within the foreseeable future. 

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