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Dean's Diet & Exercise Regime, Tips, and Motivation


Dean Pomerleau
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5 hours ago, Sthira said:

It seems strange, doesn't it? I mean, how do you mistake a niacin flush with a psilocybin experience that's powerful enough to set back anxiety and depression for six months? 

Haha - good point. I can imagine it would be hard to come up with an adequate 'placebo placeholder' in trials like these. 

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I just heard about this way of eating in a book about dementia. The author said Calorie restriction is the only thing shown to have had success with this dreaded disease.  Got my attention big time, as I am 80 years old and the fear of getting Alzheimers is my biggest nightmare.  I am currently in perfect health and take no medications whatsoever.  I have followed a low carb diet for about 10 years and my weight has remained stable.  

Went to amazon and see many books on the subject of CR ,  but have no way of knowing which is the best or how to begin.  Can you help?  How do I start?  Can you recommend any particular reading material? Do you have any members in my age range or thereabout?   

 

Judy 

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Welcome to the CR Forums Judy! 

I'm not sure there is very much evidence that CR if effective against dementia, especially Alzheimer's disease. If you can share more about what you read perhaps we can explore it.

There is certainly some evidence in rodents that lifelong CR can help with memory, but unfortunately, many of the rodent cognitive tests are confounded by the better physical shape that CR rats and mice are in when they get older. 

Moreover, it generally isnt considered a good idea to start CR in one's elder years. In rodents, late onset CR actually shortens lifespan likely due to the stress. Plus, losing significant weight or being low weight when one is older can make it harder to recover from illness or injury. Plus nutrient absorption (esp protein) decreases with age so cutting down too much on nutritious food to practice CR can be problematic. 

Here is a thread on the optimal weight for later in life:

And here is a thread on healthy eating habits to avoid dementia :

 

In general the best strategy to remain physically and mentally healthy for someone your age is to eat a healthy diet without worrying about calories and get a good amount of exercise. 

That should get you started. After you've read those feel free to ask follow up questions. 

--Dean 

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Hi Dean!

I don't completely agree with you.  I'm 83, do vigorous daily exercise, and am on a stricter CR diet than ever.  I teach full time at the University of Rochester, including a favorite graduate course in my favorite advanced topic in algebra (and also Freshman calculus😑).

Of course, i'm just a single example; it might not be the same for everyone.

I agree with you that starting CRON at a late age is a bad idea; but, if you've been on CRON from youth or middle age, it's probably a good idea to continue -- especially if you enjoy it, as I do.

If you keep up your present diet (or your earlier more rigorous one), I have little doubt that you should be able to continue with CR as you age

 

 

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Dean, thanks for quoting the interesting graph posted by MR. If we examine only non-smokers (if smokers, ,it's so much easier to increase one's longevity simply by ceasing smoking), that's what the data tell me.

 

image.png.6201d9f12bec0975d01be89d66169ddc.png

 

THe simple, obvious gist of the graph is that there is a significant increase in death only for BMIs>30. Obesity seems to be a driver of increased death. Being overweight (BMI=28) is only marginally riskier, with only 1.5/1000 deaths higher than the optimum at about BMI 24.

The data also tell us that at low BMIs (About 19) the variability in deaths is higher, so here individual factors may govern, like those cited by Dean (crappy diets in thin people, underlying illness and so on).

Last but not least, these are data which probably are not valid for people like CRers with very low adiposity nor for people with higher than average muscular mass. 

Also, data are not stratified by age, so it is not possible to give further advise to Judy beyond those already given by Dean.

My personal advice would be to insist on exercise but very, very progressively and very, very carefully. Bones' growth is stimulated by muscular stress and bone strength is vital to survival.

I would insist on the words progressively and cautiously and the best would be to hire a personal trainer specialized in elder people, at least at the beginning. That would be a good investment in longevity. Alternative is to join soem groups of elder people at the local gym.

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On 9/13/2022 at 6:53 AM, Dean Pomerleau said:

I'm not sure there is very much evidence that CR if effective against dementia, especially Alzheimer's disease. If you can share more about what you read perhaps we can explore it.

There's quite a bit on this, specifically on AD, including multiple studies in transgenic AD mouse models and reductions in Abeta in nonhuman primates (PMID 17183154).

On 9/13/2022 at 6:53 AM, Dean Pomerleau said:

There is certainly some evidence in rodents that lifelong CR can help with memory, but unfortunately, many of the rodent cognitive tests are confounded by the better physical shape that CR rats and mice are in when they get older. 

That's certainly true in some cases, like the Morris water maze, but there are plenty of other studies that don't involve physical condition at all — the extreme case being a standard contextual memory test that measures whether the mice freeze up when exposed to a stimulus they (should) have learned to associate with a coming shock.

On 9/13/2022 at 6:53 AM, Dean Pomerleau said:

Moreover, it generally isnt considered a good idea to start CR in one's elder years. In rodents, late onset CR actually shortens lifespan likely due to the stress.

Your memory of the literature is failing you — perhaps because you quit CR 😉 . Steven Spindler proved that this wasn't true if CR was done properly in 2004:

https://www.pnas.org/doi/full/10.1073/pnas.0305300101

... and has subsequently been independently confirmed in numerous other studies by other groups, such as:

https://doi.org/10.1016/j.cell.2020.02.008

https://doi.org/10.1109/IEMBS.2007.4352809

https://doi.org/10.1093/cvr/cvq273

https://doi.org/10.1038/s42255-019-0121-0

On 9/13/2022 at 6:53 AM, Dean Pomerleau said:

Plus, losing significant weight or being low weight when one is older can make it harder to recover from illness or injury. Plus nutrient absorption (esp protein) decreases with age so cutting down too much on nutritious food to practice CR can be problematic. 

 

I certainly agree that CR is much riskier when started in older adults, and granted that CR is already an experimental and risky intervention when started in young people, starting it at advanced ages would have to be considered very carefully indeed. Additionally, today there are numerous pharmacological options with a lower level evidence than CR but still good evidence as potential anti-aging interventions that don't have as many known risks to older adults.

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Hi Michael!

Nice to hear from you. I hope all is well with you. I hope the SENS Foundation is soldiering on effectively and still a good place to be despite the recent dust up...

5 hours ago, Michael R said:

There's quite a bit on this, specifically on AD, including multiple studies in transgenic AD mouse models and reductions in Abeta in nonhuman primates (PMID 17183154).

Huh, I thought you would have seen this Ingram and Mattison study [1] previously or at least done a cursory web search to see if there is anything more recent than your 2006 squirrel monkey study also by Ingram and Mattison (PMID 17183154). This 2020 study [1] found that amyloid buildup was NOT attenuated by long-term CR based on post-mortem observations done on the NIA lifelong CR monkeys.

Perhaps not surprisingly given the serious doubt recently uncovered about the relevance of amyloid beta buildup as a causal factor in AD, rhesus monkeys in both the CR and control groups had a building of amyloid beta with age, but no change in cell density with age or treatment. As the authors said, "even in the oldest-old rhesus macaques, amyloid beta plaques do not lead to overt neuron loss."

In short, I stick by my assertion that the evidence is lacking that CR has shown any benefits in a credible model of AD, which we don't have. Mouse models don't cut it, nor do mouse or monkey models that show reductions in (quite plausible irrelevant anyway) level of amyloid beta, which the lifelong NIA monkey CR study failed to show anyway.

5 hours ago, Michael R said:

Your memory of the literature is failing you — perhaps because you quit CR 😉 . Steven Spindler proved that this wasn't true if CR was done properly in 2004:

https://www.pnas.org/doi/full/10.1073/pnas.0305300101

... and has subsequently been independently confirmed in numerous other studies by other groups, such as:

https://doi.org/10.1016/j.cell.2020.02.008

https://doi.org/10.1109/IEMBS.2007.4352809

https://doi.org/10.1093/cvr/cvq273

https://doi.org/10.1038/s42255-019-0121-0

Haha - good one Michael.

Seriously, you think this is evidence? The first three of the five studies you link to started CR in mice and rats at middle-age or earlier (18 months). So they are irrelevant for the OP, who is 80 years old and thinking about starting CR.

The second to last reference above started CR in rats at 24 months. The average Sprague-dawley rat lives 3 years, and [2] says 13.2 rat days is equivalent to one human year. So starting CR at 24 months in Sprague-dawley rats is equivalent to 24*30/13.2 = 54.5 years old in humans. Again, totally irrelevant for someone who is considering starting CR at 80 years old, which (sadly) is about the life expectancy of people.

If that isn't enough to discourage the OP and show the irrelevance of your citations, the last of the five studies you linked to (https://doi.org/10.1038/s42255-019-0121-0) found the following:

Female mice aged 24 months were switched from an ad libitum (AL) diet to DR or vice versa. Strikingly, the switch from DR to AL acutely increases mortality, whereas the switch from AL to DR causes only a weak and gradual increase in survival, suggesting the body has a memory of earlier nutrition.

[3] says 24 months in mice is about 69 years old in humans - so pretty old but still more than ten years younger than the OP. So if this mice data generalize to people, it could kill you to switch from AL to CR starting at the equivalent of age 69, and going the other way (AL -> CR) provides little longevity benefit starting at age 69, to say nothing of 80!

Quite a ringing endorsement for taking up CR late in life...

5 hours ago, Michael R said:

I certainly agree that CR is much riskier when started in older adults, and granted that CR is already an experimental and risky intervention when started in young people, starting it at advanced ages would have to be considered very carefully indeed. Additionally, today there are numerous pharmacological options with a lower level evidence than CR but still good evidence as potential anti-aging interventions that don't have as many known risks to older adults

Finally a little reality on the risk of starting CR when one is elderly. I'd love to hear what generally-accessible pharmacological agent you consider to have "good evidence as potential anti-aging interventions". I'm skeptical, and I see you wisely qualified your statement with the weasel word "potential".

Always nice to engage with you Michael! I hope your post wasn't a "one and done."

--Dean

--------------
[1] Geroscience, 02 Sep 2020, 42(6):1733-1749
DOI: 10.1007/s11357-020-00259-0 PMID: 32876855 PMCID: PMC7732935

Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques.

Stonebarger GA1, Urbanski HF1, Woltjer RL2, Vaughan KL3, Ingram DK4, Schultz PL5, Calderazzo SM5, Siedeman JA5, Mattison JA3, Rosene DL5, Kohama SG6

Abstract 
As human lifespan increases and the population ages, diseases of aging such as Alzheimer's disease (AD) are a major cause for concern. Although calorie restriction (CR) as an intervention has been shown to increase healthspan in many species, few studies have examined the effects of CR on brain aging in primates. Using postmortem tissue from a cohort of extremely aged rhesus monkeys (22-44 years old, average age 31.8 years) from a longitudinal CR study, we measured immunohistochemically labeled amyloid beta plaques in Brodmann areas 32 and 46 of the prefrontal cortex, areas that play key roles in cognitive processing, are sensitive to aging and, in humans, are also susceptible to AD pathogenesis. We also evaluated these areas for cortical neuron loss, which has not been observed in younger cohorts of aged monkeys. We found a significant increase in plaque density with age, but this was unaffected by diet. Moreover, there was no change in neuron density with age or treatment. These data suggest that even in the oldest-old rhesus macaques, amyloid beta plaques do not lead to overt neuron loss. Hence, the rhesus macaque serves as a pragmatic animal model for normative human aging but is not a complete model of the neurodegeneration of AD. This model of aging may instead prove most useful for determining how even the oldest monkeys are protected from AD, and this information may therefore yield valuable information for clinical AD treatments.

------------
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733029/#!po=65.6250

[3] https://www.jax.org/news-and-insights/jax-blog/2017/november/when-are-mice-considered-old

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On 9/26/2022 at 7:39 PM, Dean Pomerleau said:

I'd love to hear what generally-accessible pharmacological agent you consider to have "good evidence as potential anti-aging interventions". I'm skeptical, and I see you wisely qualified your statement with the weasel word "potential".

Just for fun I'll guess that it's something David Sinclair has mentioned 😉

 

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On 9/27/2022 at 1:39 AM, Dean Pomerleau said:

I'd love to hear what generally-accessible pharmacological agent you consider to have "good evidence as potential anti-aging interventions". I'm skeptical, and I see you wisely qualified your statement with the weasel word "potential".

....just from a casual (but not neccessarily causal) read of the literature, and assuming you mean small molecules and including delay of aging, not reversal (I can gather the sources - if desired - for a certain claim below):


1. Rapamycin

Based on the NIA studies in mice and the assumption, that the data translates to humans. A lifespan study in non-human primates is ongoing and will finish in 2 years (preliminary data indicates that it is not working in the monkey cohort).

Caveat: the dosing and blood level of mice is far, far above what some people are taking. The "common" use of 5 mg per week from people like Peter Attia is minimizing side effects - but results in blood levels far below those measured in mice lifespan studies.

 

2. Lowering LDL-P/Apo-B

There is now clear evidence from RCTs, that reverse cholesterol transport is happening, if the LDL concentration is falling to very low levels. The existing arteriosclerotic lesions in recent studies were actively regressing. If you want, that constitutes rejuvanation of blood vessels.

 

3. Glucosamine

Based on a range of observational studies in humans, indicating modestly lower all-cause-mortality (about 15%) for the tyical 1,5 gram dose of the sulfate form. In addition one mouse study showing increased average lifespan (and maximum lifespan in females). A variety of different causes of death seem to be reduced in the observational studies (cardiovascular, respiratory, infection, cancer, diabetis...) - so this could count as "anti-aging"

 

Metformin - mixed data in mice/rats; observational data in humans suffers from study designs that are not fit for purpose or are null results

Senolytics - positive data from mice; unclear if the handful of compounds commonly discussed are safe in humans as used in mice or can even in principle work in humans. Interesting, but currently less evidence than for Rapa.

Spermidine/CKG - preliminary positive data from mice/rats + a small observational study for Sperm; but much less comprehensive than for Rapa or Gluco.

 

 

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