Spliceosomes are super-relevant too given how they are upstream of everything else (William Mair has shown that dysregulation in these accelerates aging, and correcting the defects can up lifespan)
You can argue that “ER + aging”, “golgi + aging”, or any “cell process/component + aging” is going to cause some downstream effects on aging, and to fix everything, you have to “fix” the ER, fix the spliceosomes, fix the cytoskeleton, fix the golgi, fix the NPCs, fix the histones, whatever.
Yes, this can get tricky. Do you have to directly fix everything that goes wrong? If not, how do you know what damage to directly fix?
The stuff that needs to be directly targeted in the cell (ideally, before cellular structures are damaged too much) is damaged or aggregated lipids and proteins and mutations in the mitochondria. This is the primary damage that generates secondary damage to cellular structures (like cytoskeletons and nuclear transport systems). Mutations in the nucleus aren’t targeted directly but are dealt with by WILT (or whatever could cure all cancer forever) and senescent cell killing via senolytics or whatever could get rid of them. So, fixing this primary damage should prevent most of the secondary damage from ever occurring, and if lots of secondary damage has already occured (like in older people), the repair of the primary damage may allow the self-repair machinery of the cell that still works to repair itself and the rest of this secondary damage.
Yes, this can get tricky. Do you have to directly fix everything that goes wrong? If not, how do you know what damage to directly fix?
The stuff that needs to be directly targeted in the cell (ideally, before cellular structures are damaged too much) is damaged or aggregated lipids and proteins and mutations in the mitochondria. This is the primary damage that generates secondary damage to cellular structures (like cytoskeletons and nuclear transport systems). Mutations in the nucleus aren’t targeted directly but are dealt with by WILT (or whatever could cure all cancer forever) and senescent cell killing via senolytics or whatever could get rid of them. So, fixing this primary damage should prevent most of the secondary damage from ever occurring, and if lots of secondary damage has already occured (like in older people), the repair of the primary damage may allow the self-repair machinery of the cell that still works to repair itself and the rest of this secondary damage.