More a question than comment or critique. (and still reading through but will probably be over multiple reads)
The Senolytics section comes across a bit like all senescent cells are bad so if we could just kill them all we’d be doing a good thing. But my understanding is that they also play a role in healthy body functions. Is that also your understanding here?
Largely related to the above, the framing of the post seems that of body as a machine but I’m wondering if that is the best framing. Perhaps body as a ecosystem might be better. I don’t think it changes any of the main points you make (that I’ve read) but perhaps suggests following the machine metaphor might be limiting, and in some cases point in the wrong direction. Does that seem right to you?
And thanks for posting and the summarization of current state as you see it.
The Senolytics section comes across a bit like all senescent cells are bad so if we could just kill them all we’d be doing a good thing. But my understanding is that they also play a role in healthy body functions. Is that also your understanding here?
From what I’ve read, the healthy roles they play are a) during early/embryonic development and b) in wound healing. So, don’t give senolytics to embryos or people healing from wounds I guess. Also, there’s a paper (summary here) showing that it’s possible to regain the wound-healing benefit of SCs in mice that are engineered not to create SCs, just by manually applying a single growth factor that SCs secrete into wounds. So it seems unlikely that the beneficial roles of SCs are a show-stopper, particularly because those beneficial effects are more associated with short-lived SCs rather than the ones that linger and accumulate.
Largely related to the above, the framing of the post seems that of body as a machine but I’m wondering if that is the best framing. Perhaps body as a ecosystem might be better. I don’t think it changes any of the main points you make (that I’ve read) but perhaps suggests following the machine metaphor might be limiting, and in some cases point in the wrong direction. Does that seem right to you?
I find it fascinating to think of the body as an ecosystem (e.g. cells competing for resources, occupying niches), but I use the machine analogy because it emphasizes that there’s an overall structure and function that can be degraded. What does it mean for an ecosystem to age or decline, how do you define the health of an ecosystem?
You can imagine an ecosystem <---> machine axis, where it’s more like an ecosystem when you have independent entities competing for their own survival, and more like a machine when they work more closely together to act as one. In this sense, I think metazoans are both ecosystem and machine. But much if not most of the damage that drives ageing is at the level of individual cells rather than whole organism, and it makes more sense to think of individual cells as machines.
One way in which the ecosystem view is helpful is that it emphasizes that dead or damaged cells (e.g. senescent cells) can be destroyed and replaced by the division of healthy cells. That’s something you couldn’t do in a non-ecosystem-like-machine, such as a car, and it’s a major benefit—replacement of old cells by new is really the best form of damage repair since you “repair” all the damage at once that way.
More a question than comment or critique. (and still reading through but will probably be over multiple reads)
The Senolytics section comes across a bit like all senescent cells are bad so if we could just kill them all we’d be doing a good thing. But my understanding is that they also play a role in healthy body functions. Is that also your understanding here?
Largely related to the above, the framing of the post seems that of body as a machine but I’m wondering if that is the best framing. Perhaps body as a ecosystem might be better. I don’t think it changes any of the main points you make (that I’ve read) but perhaps suggests following the machine metaphor might be limiting, and in some cases point in the wrong direction. Does that seem right to you?
And thanks for posting and the summarization of current state as you see it.
From what I’ve read, the healthy roles they play are a) during early/embryonic development and b) in wound healing. So, don’t give senolytics to embryos or people healing from wounds I guess. Also, there’s a paper (summary here) showing that it’s possible to regain the wound-healing benefit of SCs in mice that are engineered not to create SCs, just by manually applying a single growth factor that SCs secrete into wounds. So it seems unlikely that the beneficial roles of SCs are a show-stopper, particularly because those beneficial effects are more associated with short-lived SCs rather than the ones that linger and accumulate.
I find it fascinating to think of the body as an ecosystem (e.g. cells competing for resources, occupying niches), but I use the machine analogy because it emphasizes that there’s an overall structure and function that can be degraded. What does it mean for an ecosystem to age or decline, how do you define the health of an ecosystem?
You can imagine an ecosystem <---> machine axis, where it’s more like an ecosystem when you have independent entities competing for their own survival, and more like a machine when they work more closely together to act as one. In this sense, I think metazoans are both ecosystem and machine. But much if not most of the damage that drives ageing is at the level of individual cells rather than whole organism, and it makes more sense to think of individual cells as machines.
One way in which the ecosystem view is helpful is that it emphasizes that dead or damaged cells (e.g. senescent cells) can be destroyed and replaced by the division of healthy cells. That’s something you couldn’t do in a non-ecosystem-like-machine, such as a car, and it’s a major benefit—replacement of old cells by new is really the best form of damage repair since you “repair” all the damage at once that way.