5 ms·

The original paper is exhaustive and detailed, and very interesting. https://www.nature.com/articles/s41586-023-06373-1 https://www.nature.com/articles/s41586-

The original paper is exhaustive and detailed, and very interesting. https://www.nature.com/articles/s41586-023-06373-1 https://www.nature.com/articles/s41586-023-06373-1 They do a lot of analysis of human cells, but they touch on the primary issue with mice in aging studies - the life cycle of mice are fundamentally different than humans. Their life span is too short to be a comparable organism when aging is the topic of research.

RelativeDelta 3y ago
Especially relevant as the structure of aging is different relative to the rate of cellular replacement. The more frequently cells replicate the faster they accumulate transcription error. Mice have a cell doubling rate far FAR higher than humans, so we would expect a wildly different pattern in encoding.
- monero-xmr 3y ago
  When mice take over they will discover every mouse disease cured, and they won’t need mouse doctors.
  - jfoutz 3y ago
    They might be pissed when they find out the vast majority of cures kill the patient.
- aatd86 3y ago
  Reminds me that there is a whole thing about using vitamin A on the internet to have youthful skin. But I was wondering if that even was a wise thing to do given that it simply accelerate cell turnover in the epidermis if I'm not mistaken. If so, doesn't it mean premature aging of the skin? (a bit of a tangent :o)
  - qwerty456127 3y ago
    Isn't it also an anti-oxidant capable of lowering the chance of an error at any given step? I would intuitively expect lower DNA corruption rate in an individual exposed to UV (or any other kind of) radiation if they have abundance of retinol and other anti-oxidants (including tocopherol and beta-carotene) in their body.
    - aatd86 3y ago
      No clue. I have just had a cursory look and you might be right. If telomere shortening is a symptom of oxidative stress and not a cause, might well be that vitamin A could protect against aging despite accelerating cells turnover. If someone else knows more...?
      - RelativeDelta 3y ago
        Sadly unlikely. Excess Retinol concentrations do not reduce the rate of base transcription error, nor do they prevent passive oxidative stress. What they do is preempt extra-environmental stress and the resultant write error. This is less protective and more avoidive. IE, if you have less Retinol then you are genetically optimized for you will accrue slightly more oxidative stress as a result of your deficiency. Supplements can prevent this particular stress by alleviating deficiency, but they can't reduce it beyond whatever your base rate is.
        qwerty456127 3y ago
        Do I get it right you still better have slightly elevated retinol when you get exposed to excessive environmental radiation (UV or whatever, e.g. go surfing in summer in Australia or take an overseas flight) yet avoid having too much of it in other cases?
        RelativeDelta 3y ago
        Exactly correct, but perhaps not in the way you think. Having excess retinol does not offer 'protection' in the literal sense. It does not shield your DNA as it replicates to replace the cells that died at the elevated rate of death due to UV exposure. Rather, retinol is rare (% of bodymass) and is a key component of the chain of cell duplication. Having excess retinol available means your processes won't 'run out' of it when they need it. This protects from the biological equivalent of 'cutting corners' in manufacturing and THIS is how it reduces transcription error. It's preventative by way of avoiding a deprivation. If you are anticipating any excess cell death for any reason, it is better to have a slight oversupply of retinol as well as a variety of other antioxidants. The benefits are (literally) microscopic but are cumulative over a lifespan. Think of it a bit like brushing your teeth. You're not rebuilding enamel, you're preventing it's loss.
hackernewds 3y ago
Other remedies such as NMN and resviratrol have already proven in mice to work exquisitely well. Hope those will translate as more accessible solutions first, vs young boy blood transfusions.
- GreedClarifies 3y ago
  We used to hear about this all of the time circa 2010s but lately nothing. However, a number of the very rich are living quite a long time, and while they are visibly aging they are not aging as much as one would expect. This leads me to suspect that there is some kind of treatments that are expensive (like blood boys) that have some level of efficacy.
- Palmik 3y ago
  Can you clarify about resveratrol? My understanding is that the original study had issues and wasn't reproduced. This video has some details: https://youtu.be/JAFnD27ffqE https://youtu.be/JAFnD27ffqE I'm holding more hope for rapamycin, which was shown to prolong life span in mice in many studies.
- 01100011 3y ago
  Resveratrol is a crock. It is continually misrepresented by Dr. David Sinclair and his lab. Follow Charles Brenner, PhD for more info: https://twitter.com/CharlesMBrenner/status/1692333672261935560?s=20 https://twitter.com/CharlesMBrenner/status/16923336722619355...
inglor_cz 3y ago
"the life cycle of mice are fundamentally different than humans. Their life span is too short to be a comparable organism when aging is the topic of research." You know, I feel ambivalent about this. On one side, you are obviously right, mice are very different from people. On the other side, the similarities between a 2 y.o. mouse and a 80 y.o. human are striking. Grey hair, weakening muscles, cataracts, declining memory, worse organ functions across the board, hunched back, tremors, compromised immunity etc. It certainly looks like fundamentally the same process, only sped up 40 times.
- RelativeDelta 3y ago
  It functionally is. Aging is just the build-up of error in genes as microscopic write errors accumulate in successive cell epochs. It is, in short, a degenerative process marked by the failure to perfectly maintain instruction sets for the creation and maintenance of structures that allowed for survival. Reading that back it almost sounds political.
  - inglor_cz 3y ago
    "Aging is just the acclimation of error in genes as microscopic write errors accumulate in successive cell epochs." I don't think there is a scientific consensus on this particular mechanism as a root of aging. There is a lot of stuff happening along like epigenetic aging, accumulation of various toxins and seemingly pre-programmed atrophy of immune system in mammals. The only de-aging experiment that demonstrated some positive results in humans didn't touch genes at all. It was the TRIIM and TRIIM-X trial which attempted to rejuvenate the thymus and thus reinvigorate immunity. The subjects exhibit a lot of changes consistent with being a bit younger (a few years).
    - RelativeDelta 3y ago
      I am unfamiliar with "epigenetic aging". Are you talking about methylation causing worse performance in one arena or another? Immune atrophy and toxic accumulation I would read as being the terminal effects of decreased functionality as a result of error accumulation, no?

RelativeDelta 3y ago

Especially relevant as the structure of aging is different relative to the rate of cellular replacement. The more frequently cells replicate the faster they accumulate transcription error. Mice have a cell doubling rate far FAR higher than humans, so we would expect a wildly different pattern in encoding.

monero-xmr 3y ago
When mice take over they will discover every mouse disease cured, and they won’t need mouse doctors.
- jfoutz 3y ago
  They might be pissed when they find out the vast majority of cures kill the patient.
aatd86 3y ago
Reminds me that there is a whole thing about using vitamin A on the internet to have youthful skin. But I was wondering if that even was a wise thing to do given that it simply accelerate cell turnover in the epidermis if I'm not mistaken. If so, doesn't it mean premature aging of the skin? (a bit of a tangent :o)
- qwerty456127 3y ago
  Isn't it also an anti-oxidant capable of lowering the chance of an error at any given step? I would intuitively expect lower DNA corruption rate in an individual exposed to UV (or any other kind of) radiation if they have abundance of retinol and other anti-oxidants (including tocopherol and beta-carotene) in their body.
  - aatd86 3y ago
    No clue. I have just had a cursory look and you might be right. If telomere shortening is a symptom of oxidative stress and not a cause, might well be that vitamin A could protect against aging despite accelerating cells turnover. If someone else knows more...?
    - RelativeDelta 3y ago
      Sadly unlikely. Excess Retinol concentrations do not reduce the rate of base transcription error, nor do they prevent passive oxidative stress. What they do is preempt extra-environmental stress and the resultant write error. This is less protective and more avoidive. IE, if you have less Retinol then you are genetically optimized for you will accrue slightly more oxidative stress as a result of your deficiency. Supplements can prevent this particular stress by alleviating deficiency, but they can't reduce it beyond whatever your base rate is.
      - qwerty456127 3y ago
        Do I get it right you still better have slightly elevated retinol when you get exposed to excessive environmental radiation (UV or whatever, e.g. go surfing in summer in Australia or take an overseas flight) yet avoid having too much of it in other cases?
        RelativeDelta 3y ago
        Exactly correct, but perhaps not in the way you think. Having excess retinol does not offer 'protection' in the literal sense. It does not shield your DNA as it replicates to replace the cells that died at the elevated rate of death due to UV exposure. Rather, retinol is rare (% of bodymass) and is a key component of the chain of cell duplication. Having excess retinol available means your processes won't 'run out' of it when they need it. This protects from the biological equivalent of 'cutting corners' in manufacturing and THIS is how it reduces transcription error. It's preventative by way of avoiding a deprivation. If you are anticipating any excess cell death for any reason, it is better to have a slight oversupply of retinol as well as a variety of other antioxidants. The benefits are (literally) microscopic but are cumulative over a lifespan. Think of it a bit like brushing your teeth. You're not rebuilding enamel, you're preventing it's loss.

hackernewds 3y ago

Other remedies such as NMN and resviratrol have already proven in mice to work exquisitely well. Hope those will translate as more accessible solutions first, vs young boy blood transfusions.

GreedClarifies 3y ago
We used to hear about this all of the time circa 2010s but lately nothing. However, a number of the very rich are living quite a long time, and while they are visibly aging they are not aging as much as one would expect. This leads me to suspect that there is some kind of treatments that are expensive (like blood boys) that have some level of efficacy.
Palmik 3y ago
Can you clarify about resveratrol? My understanding is that the original study had issues and wasn't reproduced. This video has some details: https://youtu.be/JAFnD27ffqE https://youtu.be/JAFnD27ffqE I'm holding more hope for rapamycin, which was shown to prolong life span in mice in many studies.
01100011 3y ago
Resveratrol is a crock. It is continually misrepresented by Dr. David Sinclair and his lab. Follow Charles Brenner, PhD for more info: https://twitter.com/CharlesMBrenner/status/1692333672261935560?s=20 https://twitter.com/CharlesMBrenner/status/16923336722619355...

inglor_cz 3y ago

"the life cycle of mice are fundamentally different than humans. Their life span is too short to be a comparable organism when aging is the topic of research." You know, I feel ambivalent about this. On one side, you are obviously right, mice are very different from people. On the other side, the similarities between a 2 y.o. mouse and a 80 y.o. human are striking. Grey hair, weakening muscles, cataracts, declining memory, worse organ functions across the board, hunched back, tremors, compromised immunity etc. It certainly looks like fundamentally the same process, only sped up 40 times.

RelativeDelta 3y ago
It functionally is. Aging is just the build-up of error in genes as microscopic write errors accumulate in successive cell epochs. It is, in short, a degenerative process marked by the failure to perfectly maintain instruction sets for the creation and maintenance of structures that allowed for survival. Reading that back it almost sounds political.
- inglor_cz 3y ago
  "Aging is just the acclimation of error in genes as microscopic write errors accumulate in successive cell epochs." I don't think there is a scientific consensus on this particular mechanism as a root of aging. There is a lot of stuff happening along like epigenetic aging, accumulation of various toxins and seemingly pre-programmed atrophy of immune system in mammals. The only de-aging experiment that demonstrated some positive results in humans didn't touch genes at all. It was the TRIIM and TRIIM-X trial which attempted to rejuvenate the thymus and thus reinvigorate immunity. The subjects exhibit a lot of changes consistent with being a bit younger (a few years).
  - RelativeDelta 3y ago
    I am unfamiliar with "epigenetic aging". Are you talking about methylation causing worse performance in one arena or another? Immune atrophy and toxic accumulation I would read as being the terminal effects of decreased functionality as a result of error accumulation, no?