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As in all things biology, that's not necessarily a good thing, otherwise we would have evolved it already. Surely there are downsides (cancer, ...) > it has be

As in all things biology, that's not necessarily a good thing, otherwise we would have evolved it already. Surely there are downsides (cancer, ...) > 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 https://en.wikipedia.org/wiki/Cellular_senescence Put otherwise, there is no free lunch. Just compromises.

scotty79 3y ago
I don't know. Evolution doesn't seem to optimize for longer lifespans. So it would not optimize for substances that aid it. Long lifespan is usually not in the interest of the species. While it's very much in the interest of individual and worth pursuing.
- dist-epoch 3y ago
  You are correct. But it's also a probability distribution game. Increase probability to get cancer at advanced age, you will also increase it (maybe just a bit) for the younger population.
- amts 3y ago
  >>Evolution doesn't seem to optimize for longer lifespans. 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).
amts 3y ago
>>Surely there are downsides (cancer, ...) 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)
- dist-epoch 3y ago
  There is nothing wrong with eliminating them. But this study says psylocybin slows down cells becoming senescent, not that it eliminates them. So in fact it makes them live longer.
  - amts 3y ago
    Yep, they show it's not a senolytic, but I'd like to see an experimental human group (preferably with a dopamine transporter allele making them more prone to placebo-like responses) being given psilocybin and told that it is a senolytic. "Psilocybin treatment led to a dose-dependent decrease in cell cycle arrest markers (p21, p16, and p53) and an increase in markers of DNA replication (phosphorylated-Retinoblastoma protein; pRB) and proliferation (PCNA), as compared to vehicle-treated cells". They don't say it IS carcinogenic. At least this statement favors taking psilocybin after fasting/senolytics/autophagy induction. "may mediate SIRT1-dependent pathways which impact cellular senescence". So if senescence is delayed by it and during this period SIRTs are activated, it may be anti-cancerous.
    - dist-epoch 3y ago
      Anti-oxidants prevent cell damage caused by reactive oxygen. People thought that's a good thing. But it turns out that can actually promote cancer, because cells expect to be damaged in time, and kill themselves when that happens, and anti-oxidants mess with this mechanism. > Some of the largest clinical trials, in fact, had to be aborted because the patients receiving antioxidants had a higher incidence of cancer than patients who did not receive them. https://www.cancer.gov/news-events/cancer-currents-blog/2015/antioxidants-metastasis https://www.cancer.gov/news-events/cancer-currents-blog/2015... Preventing cellular senescence sounds like the same kind of thing, messing with an existing mechanism put in place to prevent cancer.

scotty79 3y ago

I don't know. Evolution doesn't seem to optimize for longer lifespans. So it would not optimize for substances that aid it. Long lifespan is usually not in the interest of the species. While it's very much in the interest of individual and worth pursuing.

dist-epoch 3y ago
You are correct. But it's also a probability distribution game. Increase probability to get cancer at advanced age, you will also increase it (maybe just a bit) for the younger population.
amts 3y ago
>>Evolution doesn't seem to optimize for longer lifespans. 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).

amts 3y ago

>>Surely there are downsides (cancer, ...) 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)

dist-epoch 3y ago
There is nothing wrong with eliminating them. But this study says psylocybin slows down cells becoming senescent, not that it eliminates them. So in fact it makes them live longer.
- amts 3y ago
  Yep, they show it's not a senolytic, but I'd like to see an experimental human group (preferably with a dopamine transporter allele making them more prone to placebo-like responses) being given psilocybin and told that it is a senolytic. "Psilocybin treatment led to a dose-dependent decrease in cell cycle arrest markers (p21, p16, and p53) and an increase in markers of DNA replication (phosphorylated-Retinoblastoma protein; pRB) and proliferation (PCNA), as compared to vehicle-treated cells". They don't say it IS carcinogenic. At least this statement favors taking psilocybin after fasting/senolytics/autophagy induction. "may mediate SIRT1-dependent pathways which impact cellular senescence". So if senescence is delayed by it and during this period SIRTs are activated, it may be anti-cancerous.
  - dist-epoch 3y ago
    Anti-oxidants prevent cell damage caused by reactive oxygen. People thought that's a good thing. But it turns out that can actually promote cancer, because cells expect to be damaged in time, and kill themselves when that happens, and anti-oxidants mess with this mechanism. > Some of the largest clinical trials, in fact, had to be aborted because the patients receiving antioxidants had a higher incidence of cancer than patients who did not receive them. https://www.cancer.gov/news-events/cancer-currents-blog/2015/antioxidants-metastasis https://www.cancer.gov/news-events/cancer-currents-blog/2015... Preventing cellular senescence sounds like the same kind of thing, messing with an existing mechanism put in place to prevent cancer.