If you look at our body as an information system - the errors do not necessarily persist in the same exact molecules, but they still get passed on. Newly synthesized DNA passes mutations to daugher cells. Senescent cells pass damage via SASP and increased ROS to their neighbours. Misfolded proteins disrupt homeostasis and cause more damage even if they are being degraded. When the rate of damage becomes higher than the rate of repair the process becomes exponential and irreversable.
Yep, it's a good read. Also this article doesn't show that wCIRBP is functionally different from hCIRBP, it just has a naturally higher expressjon. It would be interesting to see hCIRBP overexpression in vivo. Until then we have to rely on cold showers:)
I generally agree with aging = accumulated damage. But not only by oxygen. Whales store more oxygen in their tissues then humans, but they leave up to 200 years and raise the Peto paradox. So the answer should lay in damage prevention mechanisms. Which we don't know. So what we know, that needs to be done? Because 1000 mutations is not a practical solution.
Btw, the article below states that oxidative damage is a minor contributor to mutation burden. With the majority of mutations coming just from random deamination and replication errors.
https://www.nature.com/articles/s41586-021-03822-7
Every model is reductionist in its nature and has limitations to its application. What if we outline these limitations realistically - can we still use the model? For example, if we track cell identity during partial reprogramming, and all the major identity markers of this cell type are preserved, and the transcriptome profile 95% matches previously observed transcriptomes of this cell type? What if we train and use the model on 10-20 years intervals? This is a purely research question, since we don't have proper QC over publically provided services.
What are the examples of practical applications of Kolmogorov-Arnold if biology (models to which you can plug in variables)? If we need to pick a single most significant variable for all aging procceses, it most likely will be time.
Regarding the car example... The most often replaced parts of the car are brakes and spark plugs which have very little to do with oxidation, mostly friction and electrical errosion respectively. So even parts of simple mechanisms have different causes of aging.
Amiloids plaques are not ubiqutous among cell types, and mitochondr... (read more)