4 ms·

In terms of gaining knowledge about the most relevant mechanisms in proficient regeneration, ARF seems important, and human ARF can shut down zebrafish regenera

In terms of gaining knowledge about the most relevant mechanisms in proficient regeneration, ARF seems important, and human ARF can shut down zebrafish regeneration [1]. That implicates the evolution of cancer suppression mechanisms as the reason why most higher species are not all that great at regeneration. Further, the dance between macrophages and senescent cells during regeneration seems highly influential in the quality of regeneration, whether the path to scarring versus the path to regrowth is chosen. This is found in the few examples of proficient mammalian regeneration such as the spiny mouse [2], as well as in salamanders and zebrafish. Salamanders exhibit much more efficient creation and clearance of senescent cells in regenerating tissue, for example. [3] [1]: https://www.ucsf.edu/news/2015/11/251746/human-gene-prevents-regeneration-zebrafish https://www.ucsf.edu/news/2015/11/251746/human-gene-prevents... [2]: https://uknow.uky.edu/research/uk-researchers-identify-macrophages-key-factor-regeneration-mammals https://uknow.uky.edu/research/uk-researchers-identify-macro... [3]: http://dx.doi.org/10.7554/eLife.05505 http://dx.doi.org/10.7554/eLife.05505

toomuchtodo 8y ago
Based on your post and profile, mind if I ask a question? How much further does this move us along on human regeneration as it relates to aging?
- reasonattlm 8y ago
  One would have to speculate; it is very unclear. Proficient regeneration seems like it would be a good thing to pair with restoration of stem cell function, but without the restoration of stem cell function it might not be too helpful. As a general rule building a new human biology is hard. Even making tiny tweaks to our existing biochemistry, such as calorie restriction mimetics, is proving to be very challenging to do effectively and safely. Reverting to the known good youthful state on the other hand, is less complex. So I'd expect delivery of replacement stem cell populations to be a going concern long before adjustments that produce MRL-like or spiny-mouse-like regeneration in humans. The feature of aging that proficient regeneration seems most likely to help with is the business of fibrosis (liver, kidney, heart, lungs), where regeneration runs awry into excessive scarring, and damage to organs like the heart that do not repair themselves. Equally, it might have to be controlled very carefully in organs where structure is important, which would limit any early application. Recent experiments with cell therapy in the heart in monkeys produced disruption of heartbeat because of the formation of biological pacemarkers outside the normal parameters, for example.
  - toomuchtodo 8y ago
    Thank you for taking the time to reply.
  - fratlas 8y ago
    "replacement stem cell populations" You expect us to be able to revert the ageing process through stem cells? Any stem cells or specifically those of the host? How far off do you estimate (order of magnitude - 10/100/500 years?)
    - mkempe 8y ago
      Red/Green/Blue Mars implies that it's within the lifespan of the current generation between 30 and 50.

toomuchtodo 8y ago

Based on your post and profile, mind if I ask a question? How much further does this move us along on human regeneration as it relates to aging?

reasonattlm 8y ago
One would have to speculate; it is very unclear. Proficient regeneration seems like it would be a good thing to pair with restoration of stem cell function, but without the restoration of stem cell function it might not be too helpful. As a general rule building a new human biology is hard. Even making tiny tweaks to our existing biochemistry, such as calorie restriction mimetics, is proving to be very challenging to do effectively and safely. Reverting to the known good youthful state on the other hand, is less complex. So I'd expect delivery of replacement stem cell populations to be a going concern long before adjustments that produce MRL-like or spiny-mouse-like regeneration in humans. The feature of aging that proficient regeneration seems most likely to help with is the business of fibrosis (liver, kidney, heart, lungs), where regeneration runs awry into excessive scarring, and damage to organs like the heart that do not repair themselves. Equally, it might have to be controlled very carefully in organs where structure is important, which would limit any early application. Recent experiments with cell therapy in the heart in monkeys produced disruption of heartbeat because of the formation of biological pacemarkers outside the normal parameters, for example.
- toomuchtodo 8y ago
  Thank you for taking the time to reply.
- fratlas 8y ago
  "replacement stem cell populations" You expect us to be able to revert the ageing process through stem cells? Any stem cells or specifically those of the host? How far off do you estimate (order of magnitude - 10/100/500 years?)
  - mkempe 8y ago
    Red/Green/Blue Mars implies that it's within the lifespan of the current generation between 30 and 50.