#21

Okay I accept your argument. Pharma is making money from statins and they do marketing, so what. I don’t think Peter Attia is bought and paid for, that makes no sense. And if a pharma rep markets their drug with their study, that doesn’t change anything? If the consumer has to pay a lot for a drug, then I am annoyed.

1 Like
#22

He’s had and continues to have some very unholy alliances.

There’s no royal road. Some things are non-negotiable. You can find ways to make a whole foods plant based diet less torturous. It doesn’t have to be 100% plants and it doesn’t have to be 150 g/day of plant fibers.

I guess I am lucky in that I find most animal foods repugnant in so many ways and that I actually like vegetables. I also have decades behind me–decades in which the gap between myself and normals becomes increasingly evident, suggesting that I am probably doing some things right.

I don’t think that pharmaceuticals will ever replace eating right and exercising appropriately. They have their uses, though.

3 Likes
#23

He is just a salesman trying to sell his products.

And regarding pharma and medical profession you need to understand that pharma basically funds medical education, do you think that comes just as a philanthropic gesture? You need highly ethical doctors that have plenty of time and integrity and are willing to understand the other side. Mostly doctors are just underpaid, have no time and too many patients and are obliged to respect guidelines, scared to be sued or endanger their license and when they have most energy that are usually in debt because they had to fund their education and later their life(style) and so on… it is not that every doctor is that way but this is part of reality.

1 Like
#24

He is of course not just a salesman trying to sell his products, that is just a pessimistic over-simplification, you know that isn’t true.

3 Likes
#25

Peter seems to be eschewing endorsements and relying more on direct funding from followers. He certainly is entitled to profit from his work. Initially, I was very skeptical of him, but now I am more inclined to take his advice seriously.

3 Likes
#26

I think my biggest problem is involuntary massive caloric restriction. It makes me go nuts, pun not intended. I just have to figure out how to eat like Michael Lustgarten. He seems to have 50-100 kcal of everything, and it adds up. Small caloric restriction over time probably okay. Not a 50% caloric restriction.

2 Likes
#27

Protein restriction is bad for you
When started very very early in life protein restriction may slow mTOR-driven developmental growth, increasing longevity. Thus, methionine restriction in childhood (MR) increases lifespan in numerous species but data are conflicting. Now we know why. Lifespan may be limited either by poor fitness or by aging. MR decreases fitness but slows mTOR-driven aging. MR decreases body temperature, IGF-1 and glucose levels and deactivates the AKT/mTOR pathway in normal mice {Barcena, 2018 #87}. MR decreases fitness but slows aging. In normal mice, MR slows growth and weight gain and increases risk of death in the first year of live (Fig in Miller). Some MR mice died from rectal prolapse, which is not an age-related disease {Miller, 2005 #71}. But surviving mice lived longer because MR slows growth and aging, which is a contituation of growth. (Note: the authors’ conclusion was different but their data support my re-interpretation). Similarly, sulfur amino acid restriction (SAAR) decreases levels of Insulin and IGF in rats {Nichenametla, 2020 #88}, thus slowing growth and aging. SAAR-induced lifespan extension occurs at the cost of growth. It prolongs life span dramatically, when started early in life. In old mice group, its longevity effect is not even statistically significant ( p=0.0504) and 5 times less than in young mice group {Nichenametla, 2020 #88}. This result is consistent with the notion that aging is a quasi-program of developmental growth. (Note: the authors’ conclusion was different but their data support my re-interpretation). In Drosophila essential amino acids (EAA) shortens lifespan and rapamycin prevented this effect. In other words, EAA decrease longevity by activating mTOR. Yet, EAA increases fitness and heat stress resistance, also by activating mTOR-dependent (abrogated by rapamycin) {Emran, 2014 #77}
For us, adult humans: Combine protein diet with rapamycin

image
image1125×666 115 KB

https://x.com/blagosklonny/status/1703353087795019783?s=46

7 Likes
#29

I don’t know why protein would be different than so many other factors in health and aging. Too little and too much are suboptimal. So what is the right amount of protein?

What life do you want to live, and what body do you need to live it? There is more to life than having massive muscles just like there is more to life than living as long as possible.

I choose to live as long as I can as a strong, energetic athletic man. I need more than the minimum amount of protein that a less active, less strong person would need, I’d guess. But eating more than I need for my goal is probably too much and detrimental in one or more ways without any advantages in building / maintaining the body I want.

I don’t think this perspective gets discussed enough.

5 Likes
#30

I’m with you on the trade-offs you mention

Would just add that there is some, non-immaterial probability that we will see tremendous advances in science, technology and medicine in just the next 15-25 years

And that the probability therefore is not immaterial that if one is healthy enough at that time to intercept those advances one might achieve significantly increased longevity AND health (perhaps even rejuvenated towards a young/er version of one’s own health and vigor).

As such, this additional trade-off leads me to err more towards longevity optimization than to current/near term health maximization (on aspects where those two might contradict each other).

3 Likes
#31

Good points. While I’m skeptical of the “singularity” happening anytime soon, there is a positive trend in the longevity field of more investment, more people involved, and faster progress, so acceleration in the field may be a real possibility with increasing gains…

Of course translating research into actionable and cost-effective therapeutics with FDA approval are a whole other thing… so we’ll see. But I’m positive.

3 Likes
#32

It’s a reasonable position. Options are good … if I can learn to enjoy behaviors that give me long term options I’ll do it. If I have to suffer to get long term options that might not payoff, then I won’t.

1 Like
#33

A new paper (open access):

Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles

Calorie restriction (CR) and treatment with rapamycin (RM), an inhibitor of the mTORC1 growth-promoting signaling pathway, are known to slow aging and promote health from worms to humans. At the transcriptome and proteome levels, long-term CR and RM treatments have partially overlapping effects, while their impact on protein phosphorylation within cellular signaling pathways have not been compared. Here we measured the phosphoproteomes of soleus , tibialis anterior , triceps brachii and gastrocnemius muscles from adult (10 months) and 30-month-old (aged) mice receiving either a control, a calorie restricted or an RM containing diet from 15 months of age. We reproducibly detected and extensively analyzed a total of 6960 phosphosites, 1415 of which are not represented in standard repositories. We reveal the effect of these interventions on known mTORC1 pathway substrates, with CR displaying greater between-muscle variation than RM. Overall, CR and RM have largely consistent, but quantitatively distinct long-term effects on the phosphoproteome, mitigating age-related changes to different degrees. Our data expands the catalog of protein phosphorylation sites in the mouse, providing important information regarding their tissue-specificity, and revealing the impact of long-term nutrient-sensing pathway inhibition on mouse skeletal muscle

https://www.nature.com/articles/s42003-024-06679-4

2 Likes
#34

So seems like we may want some of both?

2 Likes
#35

Interesting paper from Healthspan on high protein diets…I have a podcast coming out soon on balancing muscle and longevity. Protein plays a role but not a key role, surprisingly.

2 Likes
#36

This perspective of protein optimization was part of Peter Attia’s manifest 10+ years ago. Now he went from protein optimization to protein maximization, following a logic according to which muscle development and efficiency rules supreme over all other factors.
Optimization is not discussed very much because it’s a tricky concept, not easily applicable in practice.
Maybe the easiest but not the most precise way would be to eat the minimum amount of protein that does not cause a decrease of appendicular muscle mass, as measured by a taylor’s tape around biceps and thighs. Even better, the minimum amount of protein which can result in hypertrophy with an adequate regime of resistance exercise.

2 Likes
#37

Agreed. I think the topic has been overwhelmed by the discussion of maximum muscle building combined with anabolic resistance. It’s also good for bones. The answer is obviously to eat a lot of protein. It is also satiating. It’s the good macro.

Unless it isn’t. I don’t know but I can see the wisdom in being careful to not overdo anything. I’m cutting my protein intake in half starting last weekend. We’ll see if I start shrinking.

FMD is going to be another part of my program….as long as it works.

1 Like
#38

U shape curve to benefits of exercise. He also mentions that a lot of people overdo exercise and that people who exercise moderately get benefits.

1 Like
#39

Always be wary of u-shapes.

2 Likes
#40

I haven’t met too many of these crazy people. I have met a few…mostly triathletes. People who go running with bone fractures to avoid losing fitness.

But there is that pesky U shape to answer for…

I have a podcast coming out soon that suggests one reason why exercise can be a mixed bag for longevity is the customary way athletes breathe. Orally vs nasally.

Mouth breathing results in overbreathing which doesn’t bring in more O2 but does blow off extra co2. The result of overbreathing is low co2 which constricts blood vessels which (may) lead to low oxygen in the heart (scarring) and elsewhere.

In addition, a lack of air filtering while breathing a lot during exercise results in damage to the lungs from dry (and cold) air, and particles and viruses that weren’t caught in the nasal passages (in mucus). This can lead to a higher rate of illness (cumulative viral load).

I am trying to adapt to 100% nasal breathing during exercise right now. It is hard but I will do it.

4 Likes
#41

Are you mouth taping for sleep? I think that goes a long ways for oral health. And I also think my daytime and exercise nose breathing has become more habitual due to the night time taping.

1 Like