It is a very interesting theory and it seems to me better supported than those previously raised.
Ageing is widely believed to reflect the accumulation of molecular damage due to energetic costs of maintenance, as proposed in disposable soma theory (DST). Here we use agent-based modelling to describe an alternative theory by which ageing could undergo positive selection independent of energetic costs. We suggest that the selective advantage of aberrant cells with fast growth might necessitate a mechanism of counterselection we name selective destruction that specifically removes the faster cells from tissues, preventing the morbidity and mortality risks they pose. The resulting survival advantage of slower mutants could switch the direction of selection, allowing them to outcompete both fast mutants and wildtype cells, causing them to spread and induce ageing in the form of a metabolic slowdown. Selective destruction could therefore provide a proximal cause of ageing that is both consistent with the gene expression hallmarks of ageing, and independent of accumulating damage. Furthermore, negligible senescence would acquire a new meaning of increased basal mortality.
https://www.sciencedirect.com/science/article/pii/S0047637422000914?via%3Dihub#bib20
The same authors have published a new article expanding the scope of the theory and explaining some antiaging interventions, including rapamycin, they will also state that the only interventions with rejuvenating potential are yamanaka factors and parabiosis.
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Excellent paper, one which I will give a deep read.
I enjoy papers that like to go against the grain of whatās currently believed. I have always read that fast metabolism may contribute to aging, this seems to argue the opposite. I liked this article very much. The puzzling thing to me is that it appears to easily explain how their method applies to CR, but seem to say that although Rapamycin clearly slows aging, it seems to buck their model. I know they try to explain how it may fit their model, but it doesnāt actually seem to exactly āfitā their model like CR.
Great stuff, thank you for sharing!
I donāt know what is true but I thought the Blagosklonny model was truly eye opening as a new model of thinking. In other words, itās not fast or slow metabolism that is better but rather the cycles of up then down. When one portion of any cycle dominates, the system breaks down. I apply this model to many things now.
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As people know I think it is the failure of cells to produce the full range of proteins that creates the aging phenotype. In part you could see the cause of this as a metabolic slow down from a less efficient set of mitochondria (plus senescence). Hence I am with them on this.
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JuanDaw
#6
The Ray Peat crowd aim for high metabolism. They want fast pulse rates, and high body temperatures.
They take in a lot of sugar. They prefer Mexican Coke, which is sweetened with cane sugar.
They also take high doses of aspirin.
Dabbled in it for a while. But the high orange juice intake increased my systolic BP. But that is an
N of 1. Many denizens swear by the Ray Peat principles.
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Thanks for that, I never even heard of the Ray Peat diet. Seems to really be outside the norm for recommended diets.
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I followed Peat for several years. He has (had) some really interesting ideas that I think should be explored more seriously. But itās also a bit of a cult. Most of his research stopped decades ago, and among his followers ANY suggestion outside of dogma is met with derision. Thereās also a ton of cherry picking when it comes to research. If a study suggests sugar isnāt great for you, for example, itās clearly a terrible study, sponsored by Big Pharma etc etc.
The Mexican Coke thing came from an interview where he was asked what he ate that day. When he included a Mexican Coke everybody went wild and itās almost required now. His objection to āregularā Coke isnāt the high fructose corn syrup btw - he likes high fructose in principle though suspects itās not pure from its synthesis, and because water in Mexico usually doesnāt have many additives like fluoride.
I think the core ideas are quite valuable and make sense when you dig into them: estrogen/serotonin are stress hormones and are Bad. Thyroid metabolism and supporting it is incredibly important (itās indeed crazy that ACTUAL thyroid hormones like T3 are rarely measured - TSH is a pineal hormone). Sugar is the bodyās primary fuel. Polyunsaturated fatty acids (PUFAs) are very, very bad while saturated fats (eg, coconut) are wonderful. Leaky gut is important. Liver and milk are excellent foodsā¦ thereās lots more but Iāll stop there. Iām happy to try to clarify some of that if I can.
I still go to the site occasionally when digging into a topic, but itās a swamp of conspiracy theory and right-wing paranoia. Huge Trump following, rabid antivax nonsense, Drs are ignorant robots, lots of QAnon BS and so on. Even a flat earth forum (I was kicked off for a while because I laughed at them - I thought it was a joke). If that stuff floats your boat then great, but for me when half the users are drowning in nonsense it kind of tarnishes their dietary/medical advice. But there ARE a small number of very smart people who donāt engage much with that stuff, and Iāll log in once a year or so to see what they might say on a topic.
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@lukegadget Iām impressed by your patience. I not wise enough yet to tolerate floating in an ocean of sh*t waiting for a fresh fish. My rule is to save myself at the first or second sign of crazy. And Iām willing to miss out on some leading edge discoveries for a while to avoid losing my focus. What do you think of Jack Kruse?
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Jack Kruse?
Not likely to follow him.
This from the first page of my landing spot:
āThen two years later, in 2018 the study from the University of Toledo proved my response to Aspreyās claims were fraudulentā
The thing is, I am 82 so I have at least beat the predicted avg age of death for the year I was born: 1941, male life expectancy ~71 years.
So, I take every diet, every protocol with a grain of salt.
People have lived to be a ripe old age on every diet imaginable.
New and controversial aging theories pop up daily.
Some people swear by and thrive on a vegetarian diet, while others swear by their carnivore diet. People get good results from a wide variety of exercises, etc.
So, when someone says āThis is the wayā, I am skeptical.
Right now as a self-experimenter, I am always looking for the most efficient way, with the least amount of physical and monetary expenditure, to improve my healthspan and life expectancy.
I am constantly tweaking my supplements, diet, exercise, and adjunct protocols such as red light therapy.
But, I almost agree with Joseph_Lavelle; āMy rule is to save myself at the first or second sign of crazyā. I try to leave at the first sign of crazy.
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Now THATās a blast from the past! Maybe 2008-10 or so. I encountered Kruse when I was trying Paleo/keto/whatever and he sometimes participated in a small Facebook group I was part of. I honestly donāt remember a single thing about his ideas, except my impression was he was a quack/crank with a lot of fan boyz. Hope Iām not offending anyone here with thatā¦
I started Peat interest around 2011, after a bout of keto dieting (as a weird aside, did anyone experience that being āfat optimizedā also means one is alcohol optimized? Basically, all the fun and none of the toxicity? And that it was glorious while it lasted? I havenāt found a good explanation for this but it would be fascinating to replicate it without the damage of an extreme diet)
Back then, the forum wasnāt nearly as skanky - the swampy politics came in later and I eventually got tired of being accused of āshillingā for Big Pharma and/or George Soros, or being shown demeaning images of black people.
Truly, I wouldnāt touch the Ray Peat Forum today unless one was first clear on the ideas by reading some of his articles at raypeat.com - he died a couple years ago but itās still up. And avoid the āconsultantsā - yahoos who know nothing about medicine but eager to dispense medical advice for a fee.
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blsm
#12
@lukegadget, thatās how I learned about rapamycin. Possibly from you?
I didnāt know about Rapa until after those phases, so probably not. Were you in those groups around then?
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blsm
#14
Yes, starting about the end of 2013.
