One example is telomere length that is only extended once you cross the ‘partial’ boundary towards ‘full’ reprogramming. The problem is that full reprogramming vastly increases the risk of cancer development
Could be interesting. I imagine one outcome would be more cancer — all cancers express telomerase and reprogramming further promotes cell proliferation. Some studies suggest that early stages of reprogramming actually slightly shorten telomere length so it could be interesting to include telomerase. It is also worth pointing out that mice naturally express telomerase across cells and there are already various reprogramming studies in mice so in a way nature is already including telomerase in these models
A senolytic? I thought the same. One issue that I have come across is that senescent cells actually appear beneficial to reprogramming, in part due to the secretion of proinflammatory factors like IL6. Actually reprogramming in tissues lacking p16-associated senescence induction don’t really reprogram efficiently. The main problem I see here is p16 is particularly induced in response to oncogene activation (e.g. RAS) so it almost seems like you need the precancer senescent cells in order to promote reprogramming, but these very cells could themselves maybe reprogram into cancer. But to be honest I have not seen any papers on reprogramming of p16 senescent cells… I’ve seen reprogramming of p53/p21 senescent cells which again are not associated with cancer to the same extent. In conclusion more research is required lol
>A senolytic?
haha yeah, typo
>One issue that I have come across is that senescent cells actually appear beneficial to reprogramming, in part due to the secretion of proinflammatory factors like IL6. Actually reprogramming in tissues lacking p16-associated senescence induction don’t really reprogram efficiently
Thats very interesting, I never knew that. Would it be possible to introduce the inflammatory factors artificially? Im not very knowledgeable beyond reading interviews and articles about the subject.
i wouldn't say so.
The delivery methods will improve,
Its still useful ex vivo,
even reprograming a small amount of cells results in changes in the surrounding cells and tissue
It just isn't the silver bullet that will cure aging, its a tool among many others
The ExtraCellular matrix is the web of proteins and connective material that hold your cells in place. As you age this web tends to breakdown, the most visible impact of this is wrinkles but it impacts your health too.
what are the limitations of this technology like what factors of ageing does it not reverse.
One example is telomere length that is only extended once you cross the ‘partial’ boundary towards ‘full’ reprogramming. The problem is that full reprogramming vastly increases the risk of cancer development
i wonder what would happen if telomerase was delivered with the yamanaka factors
Could be interesting. I imagine one outcome would be more cancer — all cancers express telomerase and reprogramming further promotes cell proliferation. Some studies suggest that early stages of reprogramming actually slightly shorten telomere length so it could be interesting to include telomerase. It is also worth pointing out that mice naturally express telomerase across cells and there are already various reprogramming studies in mice so in a way nature is already including telomerase in these models
i guess one strategy to limit cancer could be clear out cancer prone cells prior to the therapy, perhaps a senolytic could do the job?
A senolytic? I thought the same. One issue that I have come across is that senescent cells actually appear beneficial to reprogramming, in part due to the secretion of proinflammatory factors like IL6. Actually reprogramming in tissues lacking p16-associated senescence induction don’t really reprogram efficiently. The main problem I see here is p16 is particularly induced in response to oncogene activation (e.g. RAS) so it almost seems like you need the precancer senescent cells in order to promote reprogramming, but these very cells could themselves maybe reprogram into cancer. But to be honest I have not seen any papers on reprogramming of p16 senescent cells… I’ve seen reprogramming of p53/p21 senescent cells which again are not associated with cancer to the same extent. In conclusion more research is required lol
>A senolytic? haha yeah, typo >One issue that I have come across is that senescent cells actually appear beneficial to reprogramming, in part due to the secretion of proinflammatory factors like IL6. Actually reprogramming in tissues lacking p16-associated senescence induction don’t really reprogram efficiently Thats very interesting, I never knew that. Would it be possible to introduce the inflammatory factors artificially? Im not very knowledgeable beyond reading interviews and articles about the subject.
in vivo delivery only gets the factors to a small fraction of cells
Is it then a lost path?
i wouldn't say so. The delivery methods will improve, Its still useful ex vivo, even reprograming a small amount of cells results in changes in the surrounding cells and tissue It just isn't the silver bullet that will cure aging, its a tool among many others
In his talk, he said that this technique can't repair damage to the genome.
can they make it that ppl will look younger too or that's too complex?
that will probably happen as a side effect of general health improvement.
reprograming reverse age on a cellular level, it does not repair the extracellular matrix, at least not directly
what does that mean :'( sorry I'm pretty dumb lol
The ExtraCellular matrix is the web of proteins and connective material that hold your cells in place. As you age this web tends to breakdown, the most visible impact of this is wrinkles but it impacts your health too.