As with most new insights into the complexities of the human organism, things usually prove to be more complicated that they first seem. Even a cursory look at genetics reveals that in very short order. And for those hoping to use Occam's Razor to make such organic complexity seem simple, it may be more likely that they will find that Ocam's principle has caused them to slash their wrists instead.
The LiveScience Article linked below described new research that indicates that senescent cells play a role in repairing damaged lung cells by signalling stem cells. However, the action on bone healing indicates the opposite. These closing comments from the article sum up that dilemma:
What this means for anti-aging drugs
While senolytics have been shown to mess with healing in the lungs and skin, some labs have found that the drugs speed up healing in fractured bones. So what gives?
"Is bone different from lung and skin? Possibly," said Dr. Sundeep Khosla, the leader of Mayo Clinic's Osteoporosis and Bone Biology Laboratory, who oversaw one of the previous bone studies. But Khosla favors another hypothesis.
In the lung and skin studies, researchers gave the senolytics every day, but in the bone studies, there were longer breaks between doses. This strategy may hit a therapeutic sweet spot, "where there's enough inflammation for repair but not too much where you're actually starting to see negative effects," Khosla said. "In terms of clinical development of therapeutics, the devil is going to be in the dosing," he said.
The study also raises questions about what types of zombie cells senolytics target best, Khosla added.
Senescence is more like a dial than an on-off switch, so zombie cells sit on a spectrum from least to most senescent, Peng said. Zombies in aged mice seem especially inflammatory, and Peng and his colleagues are now investigating how that might affect healing.
This new information may suggest that the "hit and run" approach discussed by mateobeach in an earlier post about senolytics might really be a favored approach. Whatever the case, this research provides one more reason to be cautious about jumping into the deep end when it comes to senolytics, esp. for the combination of dasatinib and quercetin.
The LiveScience article is here (it has hyperlinks to the referenced research):
'Zombie cells' in the body tied to aging may actually help heal tissue damage, Live Science, By Nicoletta Lanese, published online 10/28/22.
livescience.com/zombie-cell...
The research paper in Science is behind a paywall, but here is a link to the Abstract:
***** A 2023 review of this post reveals that the full Science paper is now available via the link below *****
Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung , Science, Research Article / Cell Biology, 13 October 2022, Vol 378, Issue 6616, pp. 192-201
science.org/doi/10.1126/sci...
Boo!!! ciao - K9
