6 ms·

Uh oh, mice in labs are not like humans in this regard at all. Lab Mice have extraordinary cell repair capabilities. My guess is that the AKG slows down cell d

Uh oh, mice in labs are not like humans in this regard at all. Lab Mice have extraordinary cell repair capabilities. My guess is that the AKG slows down cell division. This podcast delves into the problem with lab mice and explains the trade offs that happen on an evolutionary and cellular level in mice with regards to longevity. https://www.youtube.com/watch?v=JLb5hZLw44s https://www.youtube.com/watch?v=JLb5hZLw44s

nabla9 6y ago
As a rule, all anti-aging studies and experiments lose effectiveness as the size and the natural life span of the animal used increases. It's relatively easy to dramatically increase the natural lifespan of C. elegans with gene editing, drugs or even caffeine. Mice lifespan is little harder but doable. Anything that extends healthy human lifespan more than 5% is not in the radar.
- smoyer 6y ago
  There's an organism I have seen referenced in a while ... in the first half of the last decade, my daughter who's now a doctoral candidate in human genetics at JHU did research in a lab right next door to the famous "worm shack" at UofA ( http://wormshack.ua.edu/ http://wormshack.ua.edu/).
- dcolkitt 6y ago
  My cursory understanding is that actuarial senescence (the increase in mortality rates for older populations) is not the primary driver of life span in most mammals.[1] Particularly small mammals, like lab rats. Whereas for first-world humans, it's the primary driver. Actuarial senescence makes it devilishly difficult to achieve significant life expectancy gains. Because mortality rates increase with age, life expectancy gains only scale O(sqrt(N)) with mortality reductions. Paradoxically a 40% reduction in all-cause mortality across all ages only adds 5 years of life expectancy.[2] The problem with life extension studies is small animals is that we may be measuring the wrong thing. A true breakthrough in human life spans will require slowing the rate of actuarial senescence. A wonder drug that only targets base rate mortality might double the mouse life span, but only add a few years to human life. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000432 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-and-life-expectancy/ https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-...
  - mrfusion 6y ago
    But just increasing health span would still be a huge win for humans.
jp555 6y ago
Any thoughts about how the difference in telomere length in lab-mice vs non-lab-mice might also play a role?
- sradman 6y ago
  Bret Weinstein's doctoral thesis Evolutionary Trade-Offs: Emergent Constraints and Their Adaptive Consequences [1] describes the hypothesis. Telomere length limits the number of times a cell can replicate so longer telomeres hold the potential for longer life. The trade-off is that long telomeres also allow pre-cancerous tumors to grow much larger and increase the probability of a cancer promoting mutation occurring in younger animals. [1] https://deepblue.lib.umich.edu/bitstream/handle/2027.42/63672/fruitbat_1.pdf?sequence=1 https://deepblue.lib.umich.edu/bitstream/handle/2027.42/6367...

nabla9 6y ago

As a rule, all anti-aging studies and experiments lose effectiveness as the size and the natural life span of the animal used increases. It's relatively easy to dramatically increase the natural lifespan of C. elegans with gene editing, drugs or even caffeine. Mice lifespan is little harder but doable. Anything that extends healthy human lifespan more than 5% is not in the radar.

smoyer 6y ago
There's an organism I have seen referenced in a while ... in the first half of the last decade, my daughter who's now a doctoral candidate in human genetics at JHU did research in a lab right next door to the famous "worm shack" at UofA ( http://wormshack.ua.edu/ http://wormshack.ua.edu/).
dcolkitt 6y ago
My cursory understanding is that actuarial senescence (the increase in mortality rates for older populations) is not the primary driver of life span in most mammals.[1] Particularly small mammals, like lab rats. Whereas for first-world humans, it's the primary driver. Actuarial senescence makes it devilishly difficult to achieve significant life expectancy gains. Because mortality rates increase with age, life expectancy gains only scale O(sqrt(N)) with mortality reductions. Paradoxically a 40% reduction in all-cause mortality across all ages only adds 5 years of life expectancy.[2] The problem with life extension studies is small animals is that we may be measuring the wrong thing. A true breakthrough in human life spans will require slowing the rate of actuarial senescence. A wonder drug that only targets base rate mortality might double the mouse life span, but only add a few years to human life. [1] https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000432 https://journals.plos.org/plosbiology/article?id=10.1371/jou... [2] https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-and-life-expectancy/ https://joshmitteldorf.scienceblog.com/2012/11/10/mortality-...
- mrfusion 6y ago
  But just increasing health span would still be a huge win for humans.

jp555 6y ago

Any thoughts about how the difference in telomere length in lab-mice vs non-lab-mice might also play a role?

sradman 6y ago
Bret Weinstein's doctoral thesis Evolutionary Trade-Offs: Emergent Constraints and Their Adaptive Consequences [1] describes the hypothesis. Telomere length limits the number of times a cell can replicate so longer telomeres hold the potential for longer life. The trade-off is that long telomeres also allow pre-cancerous tumors to grow much larger and increase the probability of a cancer promoting mutation occurring in younger animals. [1] https://deepblue.lib.umich.edu/bitstream/handle/2027.42/63672/fruitbat_1.pdf?sequence=1 https://deepblue.lib.umich.edu/bitstream/handle/2027.42/6367...