Interesting article on segmenting hallmarks of aging into “early”, “response”, and “late” hallmarks to better get at root causes. In particular, inflammation is shown here as a response not a root cause. Perhaps targeting chronic inflammation is only a delaying tactic (though still good). Oxidative stress is shown as a root cause.
I can provide article if Twitter isn’t an option.
What interventions target these root causes? DNA damage, epigenetic changes, membrane integrity, etc.
Inflammation can be both a cause and a response. Not mutually exclusive.
Here’s an example of inflammation assisting LDL transcytosis into the vascular endothelium. This then prompts more inflammation, as has been seen in prior studies.
Related reading (to Hallmarks):
I like this characterization, gives more meaningful targets for medicines or diet/lifestyle. Also worth noting if you look at the early causes theyre mostly linked to the direction of entropy, from a state of high order/potential to a state of lower. This can theoretically be reversed still but the difficulty is much higher than even what a lot of experts believe.
As another example, inflammaging drives gut dysfunction in aging, which further drives inflammation. It’s a deadly reinforcing system.
Improving Intestinal Inflammaging to Delay Aging? A New Perspective - ScienceDirect
Agreed. There is no doubt inflammation is a central factor to deal with, and to break the cycle of escalation. Vince Giuliano says inflammation is the key (I have an interview with him coming out in 1-2 days).
The idea of the “early” vs “late” hallmarks was to make sure to focus on what is causing inflammation in the first place. I wish I had some idea of how, beyond the basics of a healthy lifestyle. This article from Healthspan offers important ideas, including boosting autophagy.
https://gethealthspan.com/blog/articles/twelve-hallmarks-of-aging/hcioljd2ashfiualnhm2k/
Yeah, autophagy is important, at least some degree of it, since in excess it can be cancer promoting.
If rapa is like other drugs, and most likely is, then different people will have differing sensitivities, and even certain tissues could be more responsive to mTOR inhibition. This has actually been shown to be true.
Since it’s virtually impossible to accurately measure autophagic flux in humans, we’re walking a fine line with our dosing.