In dynamical system terms, I’d call the MAF scenario a single bistable feedback loop with many redundant components. (“Redundant” in the sense that many component subsets are sufficient to support the bistable feedback loop.) The senescence feedback loop is an example of this: there’s multiple components, and only a subset are needed to support the state change. For instance, either mitochondrial dysfunction or transposon activation would be sufficient to trigger the state change, and either one will cause the other once the state change is triggered.
So just because there’s one core feedback loop underlying all these core diseases, does not mean that there’s one root cause which activates that feedback loop.
There are reasons to believe there’s one root cause (or at least very few), but as you point out, these do not fully overlap with the reasons to believe there’s one core feedback loop. The main reason I expect one/few root cause(s) is that things which are out-of-equilibrium on the timescale of human aging are really rare in biological systems. The vast majority turn over much faster. So there just aren’t that many things which could be root causes.
Calorie restriction and the like do provide additional evidence, though I actually don’t think these provide particularly strong evidence for one/few root cause—not because it’s unclear whether they actually work (CR is one of the best-replicated findings in the field), but because they might just slow down the core feedback loop without directly touching the root cause(s). It is very likely that the core feedback loop itself accelerates the root cause(s), based on the exponential-acceleration pattern of the major age-related diseases, so slowing down the core feedback loop should slow down the root cause(s) too (though not reverse them or slow them down below the rate at which they progress in youth).
I like seeing how your other writing (on gears-level models, constraints, etc) seems to lie behind your approach to this research.
It was actually the other way around—I studied aging (among many other things) first, and those systems were what I drew on to understand gears, abstraction, constraints, etc.
Great comments!
In dynamical system terms, I’d call the MAF scenario a single bistable feedback loop with many redundant components. (“Redundant” in the sense that many component subsets are sufficient to support the bistable feedback loop.) The senescence feedback loop is an example of this: there’s multiple components, and only a subset are needed to support the state change. For instance, either mitochondrial dysfunction or transposon activation would be sufficient to trigger the state change, and either one will cause the other once the state change is triggered.
So just because there’s one core feedback loop underlying all these core diseases, does not mean that there’s one root cause which activates that feedback loop.
There are reasons to believe there’s one root cause (or at least very few), but as you point out, these do not fully overlap with the reasons to believe there’s one core feedback loop. The main reason I expect one/few root cause(s) is that things which are out-of-equilibrium on the timescale of human aging are really rare in biological systems. The vast majority turn over much faster. So there just aren’t that many things which could be root causes.
Calorie restriction and the like do provide additional evidence, though I actually don’t think these provide particularly strong evidence for one/few root cause—not because it’s unclear whether they actually work (CR is one of the best-replicated findings in the field), but because they might just slow down the core feedback loop without directly touching the root cause(s). It is very likely that the core feedback loop itself accelerates the root cause(s), based on the exponential-acceleration pattern of the major age-related diseases, so slowing down the core feedback loop should slow down the root cause(s) too (though not reverse them or slow them down below the rate at which they progress in youth).
It was actually the other way around—I studied aging (among many other things) first, and those systems were what I drew on to understand gears, abstraction, constraints, etc.