Cytoskeleton damage can be upstream/causal if it affects lysosomal positioning (just as anything that affects autophagy reaching the sites it needs to reach can be upstream/causal). It also affects cellular stiffness, which then affects whether molecules reach the places they should be reaching.
Lipofuscin can also be a secondary kind of damage too, and it doesn’t seem to adversely affect the cell too much until its concentration reaches a critical level.
Much of SENS was developed before the massive bioscience advances in understanding over the last 15 years—we can do better to adopt to what these new bioscience advances may imply, and there is a strong possibility that it’s much more complicated than you think it is and that damage to every single critical of the cell is somehow causally involved. I know scientists who criticize SENS on account of it underestimating the sheer complexity of the cell [and its attitude of not needing to know everything to fix damage] - while it is probably true that you don’t need to know everything to fix damage (especially if you look into low-hanging fruit like developmental biology/regeneration/stem cells/replacement organs), what SENS does right now is not sufficient
Abrupt cellular phase changes (see https://shiftbioscience.com/ and also Tony Wyss-Corey) that happen through life may be more impt than previously thought. I don’t doubt that more investment in SENS would have a high chance of producing something desireable, but there’s a high chance that the most consequential interventions may come through other routes.
That’s not the only thing that causes cytoskeleton damage.
Ultimately one path forward is: how do you create the data-set/papers that can be used by a new version of GPT-3 to suggest potential interventions for aging. That’s why ALL of the creative new technologies people use to treat genetic diseases or cancer (along with nanotechnology—yes UPenn people are already creating nanobots) can help, even if not originally designed for aging.
The point is that if the amount of tau/other junk could be kept low enough (by periodically removing it), then the accumulation of too much cytoskeleton damage should be avoided.
It’s not just tau/junk that contributes to cytoskeleton damage—the cytoskeleton is made of proteins that are easily oxidizeable in the same way that nuclear pore complexes are, and damage to NPCs don’t have tau as their primary culprit.
Cytoskeleton damage can be upstream/causal if it affects lysosomal positioning (just as anything that affects autophagy reaching the sites it needs to reach can be upstream/causal). It also affects cellular stiffness, which then affects whether molecules reach the places they should be reaching.
Lipofuscin can also be a secondary kind of damage too, and it doesn’t seem to adversely affect the cell too much until its concentration reaches a critical level.
Much of SENS was developed before the massive bioscience advances in understanding over the last 15 years—we can do better to adopt to what these new bioscience advances may imply, and there is a strong possibility that it’s much more complicated than you think it is and that damage to every single critical of the cell is somehow causally involved. I know scientists who criticize SENS on account of it underestimating the sheer complexity of the cell [and its attitude of not needing to know everything to fix damage] - while it is probably true that you don’t need to know everything to fix damage (especially if you look into low-hanging fruit like developmental biology/regeneration/stem cells/replacement organs), what SENS does right now is not sufficient
Abrupt cellular phase changes (see https://shiftbioscience.com/ and also Tony Wyss-Corey) that happen through life may be more impt than previously thought. I don’t doubt that more investment in SENS would have a high chance of producing something desireable, but there’s a high chance that the most consequential interventions may come through other routes.
Too much tau junk → too much cytoskeleton damage
Too much lipofuscin/A2E → AMD
That’s LEV’s job (SENS 2, 3, etc.).
If you still think that there’s any potential primary damage targets that SENS doesn’t specifically mention, please let me know.
That’s not the only thing that causes cytoskeleton damage.
Ultimately one path forward is: how do you create the data-set/papers that can be used by a new version of GPT-3 to suggest potential interventions for aging. That’s why ALL of the creative new technologies people use to treat genetic diseases or cancer (along with nanotechnology—yes UPenn people are already creating nanobots) can help, even if not originally designed for aging.
The point is that if the amount of tau/other junk could be kept low enough (by periodically removing it), then the accumulation of too much cytoskeleton damage should be avoided.
It’s not just tau/junk that contributes to cytoskeleton damage—the cytoskeleton is made of proteins that are easily oxidizeable in the same way that nuclear pore complexes are, and damage to NPCs don’t have tau as their primary culprit.
Mutant mitochondria.