I think you shouldn’t count aging in number of days, but rather in the number of cell divisions. (I accept there are other forms of cell damage than just division, but e.g. for telomere length division is quite an important component of aging.)
A newborn baby has fewer than 2^35 cells and an adult has fewer than 2^44 cells. Existing cells are often only replaced after 7 years, so quite a large portion of cell division happens during growth from single cell to adult.
For the sake of argument, assume that a biopsy takes 4 cells out of an 8-cell embryo, then all cells need to divide once more. So that’s 36 (or 45) divisions instead of 35 (or 44).
A significant fraction of cells turn over frequently in adults so the number of divisions for those cell types is far, far higher than 45 divisions. Those cell divisions CAN cause cancer, it a single extra cell division is going to have negligible impact on risk.
There’s an enzyme called telomerase which can extend telomeres. It’s active in embryos. So this isn’t really a concern.
Thanks! Point 2. is especially what I am interested to learn about. If there is any place where I can read more about the presence and effect of telomerase on embryos please let me know!
Also, if you have any info on these other potential issues (pathways of aging through cell division) that chat-gpt generated, I am all ears:
a. DNA Damage Accumulation: Every time a cell divides, there is a risk of errors during DNA replication. (Cells do have repair mechanisms that fix most DNA damage, and fortunately they are more capable in young cells.)
b. Mitochondrial Dysfunction: Mitochondria have their own DNA (mtDNA). Mitochondria divide independently of the cell’s nuclear DNA. However, mtDNA is more prone to damage during cell division and replication due to its proximity to reactive oxygen species (ROS) produced during energy generation.
c. Stem Cell Exhaustion: Each stem cell has a limited number of divisions it can undergo before it enters programmed cell death.
A blastocyst has an outer layer of cells (trophectoderm) and an inner mass. The trophectoderm is what becomes the placenta and the inner mass becomes the baby. The biopsy is taken from the trophectoderm.
So if anything, it sounds like the biopsy would “age the placenta” not the baby.
That’s a reasonable point… But I don’t think we can just count number of divisions either? For one thing, there are several populations of stem cells in an adult. For another, people who are 50% bigger than other people don’t live 2⁄3 as long (right? though maybe that’s not the prediction?). I think maybe embryonic stem cells protect their telomeres—not sure.
I agree my model is very simplified. (Right now I don’t know whether taking a biopsy would or would not age someone, and I’m posting here to find out.)
Interesting point that bigger people don’t die that much earlier.
I think the prediction would be that someone who is twice as big as someone else, so an adult who has say 2^45 cells instead of 2^44, would have had one extra division. Naively this would translate to 80 years / 44 divisions = ~ 2 years earlier death.
(Some short men have told me that tall men actually do die early, but when I googled papers to find out just now, that seemed false? Additionally, people with a lot of fat cells seem to die more from cancer (though the main explanation I have heard for this is that fat cells cause inflammation).)
I am quite interested in how (dangers from) cell division are different in the embryonic stage as compared to at a later stage.
I am quite interested in how (dangers from) cell division are different in the embryonic stage as compared to at a later stage.
I don’t know much about this, but two things (that don’t directly answer your question):
Generally, cells accumulate damage over time.
This happens both genetically and epigenetically. Genetically, damage accumulates (I think the main cause is cosmic rays hitting DNA that’s exposed for transcription and knocking nucleic acids out? Maybe also other copying errors?), so that adult somatic cells have (I think) several hundred new mutations that they weren’t born with. Epigenetically, I imagine that various markers that should be there get lost over time for some reason (I think this is a major hypothesis about the sort of mechanism behind various forms of aging).
This means that generally, ESCs are more healthy than adult somatic cells.
One major function of the reproductive system is to remove various forms of damage.
You can look up gametogenesis (oogenesis, spermatogenesis). Both processes are complicated, in that they involve many distinct steps, various checks of integrity (I think oocytes + their follicles are especially stringently checked?), and a lot of attrition (a fetus has several million oocytes; an adult woman ovulates at most a few hundred oocytes in her lifetime, without exogenous hormones as in IVF).
So, ESCs (from an actual embryo, rather than from some longer-term culture) will be heavily selected for genetic (and epigenetic?) integrity. Mutations that would have been severely damaging to development will have been weeded out. (Though there will also be many miscarriages.)
Wouldn’t it age them by at most 1 day (which is about how long mitosis takes)?
I think you shouldn’t count aging in number of days, but rather in the number of cell divisions. (I accept there are other forms of cell damage than just division, but e.g. for telomere length division is quite an important component of aging.)
A newborn baby has fewer than 2^35 cells and an adult has fewer than 2^44 cells. Existing cells are often only replaced after 7 years, so quite a large portion of cell division happens during growth from single cell to adult.
For the sake of argument, assume that a biopsy takes 4 cells out of an 8-cell embryo, then all cells need to divide once more. So that’s 36 (or 45) divisions instead of 35 (or 44).
You’re ignoring several facts:
A significant fraction of cells turn over frequently in adults so the number of divisions for those cell types is far, far higher than 45 divisions. Those cell divisions CAN cause cancer, it a single extra cell division is going to have negligible impact on risk.
There’s an enzyme called telomerase which can extend telomeres. It’s active in embryos. So this isn’t really a concern.
Thanks! Point 2. is especially what I am interested to learn about. If there is any place where I can read more about the presence and effect of telomerase on embryos please let me know!
Also, if you have any info on these other potential issues (pathways of aging through cell division) that chat-gpt generated, I am all ears:
a. DNA Damage Accumulation: Every time a cell divides, there is a risk of errors during DNA replication. (Cells do have repair mechanisms that fix most DNA damage, and fortunately they are more capable in young cells.)
b. Mitochondrial Dysfunction: Mitochondria have their own DNA (mtDNA). Mitochondria divide independently of the cell’s nuclear DNA. However, mtDNA is more prone to damage during cell division and replication due to its proximity to reactive oxygen species (ROS) produced during energy generation.
c. Stem Cell Exhaustion: Each stem cell has a limited number of divisions it can undergo before it enters programmed cell death.
New information I came across is:
A blastocyst has an outer layer of cells (trophectoderm) and an inner mass. The trophectoderm is what becomes the placenta and the inner mass becomes the baby. The biopsy is taken from the trophectoderm.
So if anything, it sounds like the biopsy would “age the placenta” not the baby.
That’s a reasonable point… But I don’t think we can just count number of divisions either? For one thing, there are several populations of stem cells in an adult. For another, people who are 50% bigger than other people don’t live 2⁄3 as long (right? though maybe that’s not the prediction?). I think maybe embryonic stem cells protect their telomeres—not sure.
I agree my model is very simplified. (Right now I don’t know whether taking a biopsy would or would not age someone, and I’m posting here to find out.)
Interesting point that bigger people don’t die that much earlier.
I think the prediction would be that someone who is twice as big as someone else, so an adult who has say 2^45 cells instead of 2^44, would have had one extra division. Naively this would translate to 80 years / 44 divisions = ~ 2 years earlier death.
(Some short men have told me that tall men actually do die early, but when I googled papers to find out just now, that seemed false? Additionally, people with a lot of fat cells seem to die more from cancer (though the main explanation I have heard for this is that fat cells cause inflammation).)
I am quite interested in how (dangers from) cell division are different in the embryonic stage as compared to at a later stage.
I don’t know much about this, but two things (that don’t directly answer your question):
Generally, cells accumulate damage over time.
This happens both genetically and epigenetically. Genetically, damage accumulates (I think the main cause is cosmic rays hitting DNA that’s exposed for transcription and knocking nucleic acids out? Maybe also other copying errors?), so that adult somatic cells have (I think) several hundred new mutations that they weren’t born with. Epigenetically, I imagine that various markers that should be there get lost over time for some reason (I think this is a major hypothesis about the sort of mechanism behind various forms of aging).
This means that generally, ESCs are more healthy than adult somatic cells.
One major function of the reproductive system is to remove various forms of damage.
You can look up gametogenesis (oogenesis, spermatogenesis). Both processes are complicated, in that they involve many distinct steps, various checks of integrity (I think oocytes + their follicles are especially stringently checked?), and a lot of attrition (a fetus has several million oocytes; an adult woman ovulates at most a few hundred oocytes in her lifetime, without exogenous hormones as in IVF).
So, ESCs (from an actual embryo, rather than from some longer-term culture) will be heavily selected for genetic (and epigenetic?) integrity. Mutations that would have been severely damaging to development will have been weeded out. (Though there will also be many miscarriages.)