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.
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.
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)
If someone else knows more...?
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.
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.
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.
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.
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).
Immune atrophy and toxic accumulation I would read as being the terminal effects of decreased functionality as a result of error accumulation, no?
https://www.lifespan.io/topic/why-we-age/
But there has been recent talk about adding five more:
https://www.lifespan.io/news/researchers-propose-five-new-ha...
Aging is complicated. Stuff like extracellular cross-linking of collagen through glycation cannot be reduced to genetic/epigenetic changes, and yet is obviously a huge problem for aged organisms.
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.
I'm holding more hope for rapamycin, which was shown to prolong life span in mice in many studies.