6 ms·

Somewhat related to this, elephants have around 20 copies of TP53, the master ‘protector of the genome’ gene that senses DNA damage and reacts to it. With lots

Somewhat related to this, elephants have around 20 copies of TP53, the master ‘protector of the genome’ gene that senses DNA damage and reacts to it. With lots of cells you need lots of protection against cancer. I wonder if blue whales have more. Response to somatic mutation is the name of the game for organisms with very old or very many cells.

londons_explore 5y ago
Some human cells, notably within the immune system must mutate to function. If they do not mutate, you will die as bacteria and viruses mutate faster than your defences can adapt.
- deleted 5y ago
  [deleted]
- sxv 5y ago
  This sounds interesting, do you have any references for further reading?
  - londons_explore 5y ago
    https://en.wikipedia.org/wiki/Somatic_hypermutation https://en.wikipedia.org/wiki/Somatic_hypermutation Treatments that reduce mutations in general could make the immune system less effective (increasing your chances of dying of disease, and that of passing a disease on to others). It could also cause fewer mutations in your offspring, which might hurt human evolution over many hundreds of generations. Curing cancer tomorrow, but with side effects of dramatically increasing transmission and deaths by transmissible disease, and causing humans to die out from failure to adapt to future environments seems like overall a bad plan. It's certainly something we'll need to fully understand before making use of.
    - robwwilliams 5y ago
      Not right. Get some hard core background in population genetics. If you want a great (but costly) text on this topic with real insight—, then read Lynch’s The Origins of Genome Architecture.
      - cinntaile 5y ago
        What's so good about it and how dated is it? The book is 13 years old, a lot is happening in that field no?
        deleted 5y ago
        [deleted]
- robwwilliams 5y ago
  Nope: there is a huge difference between MHC gene recombination and mutation.
medymed 5y ago
Also these 100+ year old people hit multiple genetic jackpots, avoiding diseases of suboptimal metabolism and cellular senescence as well. There are many other populations that could be analyzed: the 70+ year old relentless sunbathers with leathery skin but no skin cancers, the 90 year olds smoking 2 packs a day for 60 years with pristine lungs. Because these people don’t end up in clinics there is not necessarily as much known about their innate resilience to carcinogens or other malign influences.
- londons_explore 5y ago
  Even 100+ year old people tend to end up in healthcare settings for a short while before they die.
  - cutemonster 5y ago
    Could it be that they then don't get as thoroughly investigated, as someone else who is, say, 50 or 75 and also ends up in the hospital? The 100+ won't live that much longer anyway
- bobmaxup 5y ago
  Are there really people who have smoked two packs a day for 60 years with pristine lungs?
  - netizen-936824 5y ago
    I think the poster may have meant cancer free. I don't think its probable that a smoker wouldn't have some sort of buildup or other impairment
  - deepspace 5y ago
    No. Emphysema is pretty much a given for lifelong smokers who continue smoking past their 45th birthday.
    - imposter 5y ago
robwwilliams 5y ago
Do you have a reference? It would be hard to establish causality. Genetic drift extremely important in megafauna due to very small population size. Selection has to be exceedingly strong. Read Mike Lynch’s lovely paper in PNAS in 2007 (free from PubMed)—The frailty of adaptive hypotheses for the origin of organismal complexity. There is a high risk of “just so” stories to “explain” biological processes and phenomena. Nassim Taleb’s Black Swan well worth reading; Chapter 6 in particular.
- deleted 5y ago
  [deleted]
  - deleted 5y ago
    [deleted]
robocat 5y ago
Cancer becomes almost irrelevant as you get really old: https://flowingdata.com/2016/01/05/causes-of-death/ https://flowingdata.com/2016/01/05/causes-of-death/ Not to say that the other reasons for death are not related to mutations. Edit: also I worry I am making a selection bias - presumably extra protection from cancer may be required along with many other traits to become a centenarian (A and B and C …).
- vidarh 5y ago
  It becomes almost irrelevant as you get really old, but that is not because cancer goes away but because cancer has already killed a good chunk of those most susceptible and other causes becomes more likely to kill the remainder before cancer gets a chance.
  - robocat 5y ago
    > but because cancer has already killed a good chunk of those most susceptible Why do you think that? Death rates for cancer continue to trend upwards by age: https://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/age#heading-Zero https://www.cancerresearchuk.org/health-professional/cancer-... If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred.
    - vidarh 5y ago
      > Why do you think that? Because it is a truism. If they lived as long without cancer as everyone else, they per definition are not more susceptible. It's simply a restating of what being more susceptible implies. > If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred. This does not logically follow. This assumes that removing people with a genetic or other predisposition for getting cancer early would reduce the average risk of cancer more than increasing age increases it. Mortality rates compounds. Reducing your average risk of dying of a given cause by even a tiny proportion on a per-year basis adds up to substantial chances of surviving longer.
- medymed 5y ago

londons_explore 5y ago

Some human cells, notably within the immune system must mutate to function. If they do not mutate, you will die as bacteria and viruses mutate faster than your defences can adapt.

deleted 5y ago
[deleted]
sxv 5y ago
This sounds interesting, do you have any references for further reading?
- londons_explore 5y ago
  https://en.wikipedia.org/wiki/Somatic_hypermutation https://en.wikipedia.org/wiki/Somatic_hypermutation Treatments that reduce mutations in general could make the immune system less effective (increasing your chances of dying of disease, and that of passing a disease on to others). It could also cause fewer mutations in your offspring, which might hurt human evolution over many hundreds of generations. Curing cancer tomorrow, but with side effects of dramatically increasing transmission and deaths by transmissible disease, and causing humans to die out from failure to adapt to future environments seems like overall a bad plan. It's certainly something we'll need to fully understand before making use of.
  - robwwilliams 5y ago
    Not right. Get some hard core background in population genetics. If you want a great (but costly) text on this topic with real insight—, then read Lynch’s The Origins of Genome Architecture.
    - cinntaile 5y ago
      What's so good about it and how dated is it? The book is 13 years old, a lot is happening in that field no?
      - deleted 5y ago
        [deleted]
robwwilliams 5y ago
Nope: there is a huge difference between MHC gene recombination and mutation.

medymed 5y ago

Also these 100+ year old people hit multiple genetic jackpots, avoiding diseases of suboptimal metabolism and cellular senescence as well. There are many other populations that could be analyzed: the 70+ year old relentless sunbathers with leathery skin but no skin cancers, the 90 year olds smoking 2 packs a day for 60 years with pristine lungs. Because these people don’t end up in clinics there is not necessarily as much known about their innate resilience to carcinogens or other malign influences.

londons_explore 5y ago
Even 100+ year old people tend to end up in healthcare settings for a short while before they die.
- cutemonster 5y ago
  Could it be that they then don't get as thoroughly investigated, as someone else who is, say, 50 or 75 and also ends up in the hospital? The 100+ won't live that much longer anyway
bobmaxup 5y ago
Are there really people who have smoked two packs a day for 60 years with pristine lungs?
- netizen-936824 5y ago
  I think the poster may have meant cancer free. I don't think its probable that a smoker wouldn't have some sort of buildup or other impairment
- deepspace 5y ago
  No. Emphysema is pretty much a given for lifelong smokers who continue smoking past their 45th birthday.
  - imposter 5y ago

robwwilliams 5y ago

Do you have a reference? It would be hard to establish causality. Genetic drift extremely important in megafauna due to very small population size. Selection has to be exceedingly strong. Read Mike Lynch’s lovely paper in PNAS in 2007 (free from PubMed)—The frailty of adaptive hypotheses for the origin of organismal complexity. There is a high risk of “just so” stories to “explain” biological processes and phenomena. Nassim Taleb’s Black Swan well worth reading; Chapter 6 in particular.

deleted 5y ago
[deleted]
- deleted 5y ago
  [deleted]

robocat 5y ago

Cancer becomes almost irrelevant as you get really old: https://flowingdata.com/2016/01/05/causes-of-death/ https://flowingdata.com/2016/01/05/causes-of-death/ Not to say that the other reasons for death are not related to mutations. Edit: also I worry I am making a selection bias - presumably extra protection from cancer may be required along with many other traits to become a centenarian (A and B and C …).

vidarh 5y ago
It becomes almost irrelevant as you get really old, but that is not because cancer goes away but because cancer has already killed a good chunk of those most susceptible and other causes becomes more likely to kill the remainder before cancer gets a chance.
- robocat 5y ago
  > but because cancer has already killed a good chunk of those most susceptible Why do you think that? Death rates for cancer continue to trend upwards by age: https://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/age#heading-Zero https://www.cancerresearchuk.org/health-professional/cancer-... If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred.
  - vidarh 5y ago
    > Why do you think that? Because it is a truism. If they lived as long without cancer as everyone else, they per definition are not more susceptible. It's simply a restating of what being more susceptible implies. > If your “hypothesis” were correct, the rate of death would decline after the early fatalities occurred. This does not logically follow. This assumes that removing people with a genetic or other predisposition for getting cancer early would reduce the average risk of cancer more than increasing age increases it. Mortality rates compounds. Reducing your average risk of dying of a given cause by even a tiny proportion on a per-year basis adds up to substantial chances of surviving longer.
medymed 5y ago