> it has been suggested that cellular senescence evolved as a way to prevent the onset and spread of cancer. Somatic cells that have divided many times will have accumulated DNA mutations and would be more susceptible to becoming cancerous if cell division continued. As such, it is becoming apparent that senescent cells undergo conversion to an immunologic phenotype that enables them to be eliminated by the immune system.
https://en.wikipedia.org/wiki/Cellular_senescence
Put otherwise, there is no free lunch. Just compromises.
Long lifespan is usually not in the interest of the species. While it's very much in the interest of individual and worth pursuing.
Not quite true (if not weighting high on optimization). There are multiple species which are outliers by lifespan in their niches: whales, hydras, etc. Even within rodent family there is a wide range of lifespans typical for a species - from ~2 years for a mouse to ~30 years for a naked mole rat.
There are regenerative species with incredibly messy genomes which are biologically immortal. So relying on evolution as a main explanatory principle is not comprehensive enough (especially given that you can't currently reverse engineer much of the evolution subjects).
Me doesn't quite understand the rationale behind this widely used argument. Ok, senescent cells emerge as a mechanism to ward off cancer. They are basically semi-cancerous cells with an arrested cell division cycle ("zombies"). The goal of cancer therapies is to eliminate cancer cells. So what's wrong with the elimination of senescent cells? (especially if you get new stem cells differentiating into new healthy tissue in place of senescent ones or let the surrounding healthy tissue to proliferate there)
Therefore, in vitro (cell culture) studies like this one that only focus on psilocybin and not psilocin are limited in translational value. They fail to accurately mimic the physiological context, where psilocin, not psilocybin, would interact with these cell types. For translational relevance, we need to study the actual bioactive compound (psilocin) in systems that closely replicate human physiology. Thus, in vitro studies with psilocybin provide an inaccurate picture. I would be surprised if this made it through peer review anywhere.
The general rationale seems rather feasible, given the application of the SSRI antidepressant fluvoxamine [1] to reduce severity of COIVD infection, as James Kirkland on STEM talk from the link below mentioned that senescence also may be induced by infections.
[1] https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6...
In terms of physical properties, psilocin and psilocybin differ significantly due to this transformation. These differences have meaningful consequences at the receptor level, which is where the physiological and psychoactive effects are primarily mediated. The key concern is how the resultant psilocin molecule interacts with cellular receptors and proteins, which almost certainly differs from psilocybin's interactions.
This distinction is quite similar to drug design concepts, where seemingly minor modifications to structure can drastically alter a drug's efficacy and interactions. The difference between a phosphate group (as in psilocybin) and a hydroxyl group (as in psilocin) may appear subtle, but in pharmacological terms, this can easily distinguish between an active and inactive compound.
[1]. https://www.ihmc.us/stemtalk/episode-122/ (47:30)
