Another class of hypotheses for what's going on here: based on my admittedly-poor understanding, the spleen mainly turns over various cell types from the blood (notably including mast cells and RBCs). Presumably the body has feedback loops to maintain cell count for these cell types, so if the spleen is removed, production of these cell types should also slow/stop. I could imagine several different stories for how that might alleviate aging problems:
- to the extent that stem cell exhaustion is a thing, slowing production of cells might allow stem cell reserves to last longer
- slowed production might slow proliferation of precancerous cells
- rapid proliferation might push cells past the critical point for senescence
- ... probably lots of other possibilities I haven't thought of
This is pretty interesting. If one had access to a hospital's database, I imagine it wouldn't be hard to do a retrospective analysis looking at people who had a splenectomy and then seeing if they ended up with lower risk for cardiovascular disease. All I know is lymphocytes are implicated in the early stages of atherosclerosis. How that fact might be connected, I have no idea, but it seems it could be.
Mice used in experiments are typically really inbred; usually the JAX strain. One of the notable traits of JAX strain mice that separates them from normal mice is that their immune response is significantly more Th2-biased than normal mouse immune responses, which seems pretty relevant to any effects that might be related to mast cells, and even more relevant to any effects that might have to do with regulatory T cells.
I don't know what strains of mice were used in the splenectomy experiments that showed large lifespan increases, but unless it was wild-type mice or the experiment is reproduced with wild-type mice, my default interpretation would be that this is probably a consequence of lab mice having weird inbred immune systems.
Thank you for writing this. Very interesting and personal to me. I had my splenectomy when I was 24. That was in the early 90's. If you are in this field of research, or you know someone who is, I would be open to discussion and lab testing to help further your studies. In general, I am in good physical shape, and I have several children who are all in school - so I have a lot of incentive to live for a long time. Have a great day!
Another class of hypotheses for what's going on here: based on my admittedly-poor understanding, the spleen mainly turns over various cell types from the blood (notably including mast cells and RBCs). Presumably the body has feedback loops to maintain cell count for these cell types, so if the spleen is removed, production of these cell types should also slow/stop. I could imagine several different stories for how that might alleviate aging problems:
- to the extent that stem cell exhaustion is a thing, slowing production of cells might allow stem cell reserves to last longer
- slowed production might slow proliferation of precancerous cells
- rapid proliferation might push cells past the critical point for senescence
- ... probably lots of other possibilities I haven't thought of
This is pretty interesting. If one had access to a hospital's database, I imagine it wouldn't be hard to do a retrospective analysis looking at people who had a splenectomy and then seeing if they ended up with lower risk for cardiovascular disease. All I know is lymphocytes are implicated in the early stages of atherosclerosis. How that fact might be connected, I have no idea, but it seems it could be.
Mice used in experiments are typically really inbred; usually the JAX strain. One of the notable traits of JAX strain mice that separates them from normal mice is that their immune response is significantly more Th2-biased than normal mouse immune responses, which seems pretty relevant to any effects that might be related to mast cells, and even more relevant to any effects that might have to do with regulatory T cells.
https://www.research.uky.edu/uploads/commonly-used-mouse-strains
I don't know what strains of mice were used in the splenectomy experiments that showed large lifespan increases, but unless it was wild-type mice or the experiment is reproduced with wild-type mice, my default interpretation would be that this is probably a consequence of lab mice having weird inbred immune systems.
Thank you for writing this. Very interesting and personal to me. I had my splenectomy when I was 24. That was in the early 90's. If you are in this field of research, or you know someone who is, I would be open to discussion and lab testing to help further your studies. In general, I am in good physical shape, and I have several children who are all in school - so I have a lot of incentive to live for a long time. Have a great day!
Can we expect the same longevity effects when mice are not in captivity?
Can we consider urban humans to be in captivity for biological purposes?