Recent paper on CR

[Sibiriak]

Mechanism,  thanks for the extended informative reply!  
 

Mechanism:  ...the macronutrient percentages in the other Blue Zones are quite variable

 

It's still not clear to me that the Blue Zone macronutrient percentages are "quite variable".   Variable,  of course,  but all lying within the general framework of "high complex-carb diet with medium levels of fat and medium-to-low levels of protein

[Mechanism]

Edited

[Sibiriak]

Mccoy,   here's an overview of rapamycin I found useful  (but you are far more well-read on the subject than I am):

 

Longevity, aging and rapamycin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207939/

PMCID: PMC4207939

[mccoy]

Sibiriak, thanks for the references on Blagosklonny, he's apparently pretty much into pharmaceutical inhibition of mTOR. I'm thinking back to his article with Koschei and Baba yaga, very original and amusing.

 

I share your same limitations in the ignorance of physiology and biology, but it's evident that there is so much nutrition & health material available in the internet that everyone can hit a pretty thorough understanding of specific subjects. I also listened to quite a few podcasts on rapamycin and mTOR while driving. I find I cannot listen any longer to the news, much better listen to Rhonda Patrick, David Sabatini, Walter Longo and the likes. 

 

The Ehninger et al. article constitues a pretty exhaustive review on rapamycin studies on rats. Testicles degeneration and cataract are confirmed. But as far as I understood, the positive effects on longevity are due to the inhibition of carcinogenesis, which is actually and healthspan boosting effect.  Strangely, muscle tissue seems not to be negatively affected, although dosages were not very high according to the authors. But some parts of the cardiac muscle seem to be negatively targeted.

 

AS I've written elsewhere, some silicon valley entrepreneurs are already taking rapamycin, it seems that dosages on rats are pretty much established and immunosuppressive dosages on humans are well known. Soon antiaging dosages for dogs will be publicly available, as I read in another thread

[Sibiriak]

mccoy: But as far as I understood, the positive effects on longevity are due to the inhibition of carcinogenesis, which is actually and healthspan boosting effect.

 

That would be true for humans:  inhibiting one of several deadly diseases affecting individual lifespans would increase the healthspan and median lifespan of a group,  but it would not necessarily increase maximum lifespan. If, however, for a particular group of animals, one disease-type in particular is overwhelmingly the cause of death, then inhibiting that disease would be effectively  increase maximum lifespan.

 

In all these backgrounds and across sexes, neoplastic lesions represent a major cause of death. For example, approx. 70 % of C57BL/6 animals naturally die due to neoplastic disease with lymphomas and hematopoietic neoplasms representing the leading causes of death [43–45]. Similarly, in UM-HET3 mice, neoplastic lesions are the natural cause of death in >80 % of cases [11, 46]. Lymphomas and hematopoietic tumors also represent the most common neoplastic lesions that naturally limit life in UM-HET3 mice [11, 46]. Any intervention extending lifespan in these strains is, therefore, expected to do so primarily by counteracting these common life-limiting neoplastic pathologies.

 

Lifespan extension via inhibition of carcinogenesis is indeed a plausible scenario for rapamycin-mediated longevity effects because rapamycin has well-known anti-neoplastic properties, including inhibitory effects on de novo cancer formation, as well as suppression of established tumors via inhibition of cancer growth, promotion of apoptosis of neoplastic cells and/or a modification of the host response to the tumor (for example, inhibiting angiogenesis) [47–54]. In line with this, rapamycin was found to suppress cancers and extend life in a range of genetic early-onset cancer models, such as p53 mutant mice, Apc mutant animals, Rb mutant mice and HER-2/neu transgenic mice [55–58], strongly implicating direct anti-cancer action in the longevity effects seen in these studies.

 

Detailed cause-of-death analyses in rapamycin-treated UM-HET3 mice and controls indicated that both groups die primarily (i.e., in >80 % of cases) due to cancers, but rapamycin-treated animals do so later in life than controls [11], indicating that rapamycin postpones lethal neoplastic disease in treated animals. In the context of this study, it was not possible to determine if rapamycin also extends lifespan in those animals that die due to non-neoplastic disease because non-neoplastic disease accounted only for a small fraction (approx. 10 %) of deaths in UM-HET3 mice [11]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207939/

[emphasis added]

 

I also found this analysis useful, even if basic:

 

Lifespan extension does not necessarily indicate effects on aging. With regards to lifespan-extending interventions in mice two general scenarios are possible:

 

(a) interventions may have isolated effects on lifespan by inhibiting specific life-limiting pathology, such as cancers, without broadly modulating aging traits;

 

(b) lifespan extension occurs by inhibition of life-limiting pathologies, such as cancers, and this effect represents one aspect of a more general effect that the respective intervention has on aging.

 

During the course of aging most mammalian tissues and organ systems undergo characteristic molecular, structural and functional alterations. To assess whether a pharmacological or genetic intervention slows the rate of mammalian aging it is necessary to examine its effects on a broad range of mammalian aging phenotypes in different cell types, tissues and organ systems. Comprehensive analyses of aging traits may then identify aging traits that are ameliorated by specific genetic or pharmacological interventions.     [Or other interventions in the case of humans--Sibiriak] 

[emphasis added]

 

In any case, I’m primarily focused on my own personal  healthspan and lifespan,  rather than on longevity research per se, so the issue of median vs maximum lifespan is more theoretical than practical for me, especially in the light of the extremely limited and dicey options for max-LS extension per se.  (It's hard enough even to attain one's max-LS, whatever it is, let alone try to substantially increase it.)

 

mccoy: Since I seem to be pretty healthy, lean and  statistically at a low mortality risk, my current hobby is to lower those statistical odds and prevent, as much as possible and within reason, the oncoming of the big C (and other known killers of course).

 

[...]At the end, what would be a reasonable dietary scheme which decreases PCa risk? I'm starting a 'shopping list',

https://www.crsociety.org/topic/11395-prostate-cancer-prevention/ 

[emphasis added]

 

I’m  have similar aims and I'm asking the same questions.   Quite a few of my family members have lived into their mid-nineties with  standard diets and no special health regimes etc.  So I’m reasonably aiming to do slightly better than they did via improved diet, exercise, fasting, etc.   I’m not gunning for much more than that, and,  from my  spiritual standpoint,  I realize that it’s all essentially a kind of “controlled folly”,  to use a Carlos Castaneda expression.     

              

I’ve pretty much worked out my diet, exercise, fasting, time-restricted eating, cold exposure, yoga/qigong etc regimes-- for the time being at least.  I tend to a lot of research,  go as deep as I can, ruminate, explore, experiment, make some decisions, then move on.  There are periodic reassessments of course; keeping up with new data and new ideas.

 

Right now, I’m  mostly focused on additional dietary/supplement  approaches to preventing/ameliorating the  major age-related afflictions (cancer,  cardiovascular disease, neurodegenerative disease (cognitive decline),  sarcopenia, osteopenia, immune system senescence, hearing/vision degeneration etc.)

 

I’m not really looking into rapamycin for personal use. I have done a lot of research into turmeric/curcumin,  especially approaches to greater bioavailability.  That’s one fixture in my arsenal now.   Rhodiola (+ eleutherococcus senticosus, aka Siberian ginseng) and the general theory of adaptogens recently caught my interest.   According to Siberian folk wisdom, those who take rhodiola daily and live well will make it  to 100 years. 

 

Rhodiola rosea, Siberia, Altai mountains, Katun ridge.

 

Cf. "Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity"  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991026/

 

And, of course, there are the usual suspects:  green tea extracts, resveratrol, soy isoflavones, coffee/caffeine etc.  and a whole host of other  phytochemicals, too many to list.  Low-dose NSAIDs +gastroprotection  is an  interest as well, only theoretical at this point. Ultimately, as I said,  the idea for me is to establish some routines and habits then  move on to other interests in life. 

[Sibiriak]

mccoy:  I'm thinking back to his article with Koschei and Baba yaga

 

 

There's much talk of Baba Yaga (pronounced " iGA ") around my parts.  There have been some sightings of her recently,  in the deep in the forest usually.    Probably  just nonsense,  but I'm keeping my eye out for her during my nightly treks.    I have a few questions-- but it will cost me, that much is given.

[mccoy]

By the same authors of the study on nutritional geometry (a paper also listed by alPater, thanks al pater!):

 

New Horizons: Dietary protein, ageing and the Okinawan ratio DAVID G. LE COUTEUR1,2, SAMANTHA SOLON-BIET1,3, DEVIN WAHL1 , VICTORIA C. COGGER1,2, BRADLEY J. WILLCOX4,5, D. CRAIG WILLCOX4,5,6, DAVID RAUBENHEIMER1,3, STEPHEN J. SIMPSON1,3

 

Which carries practical suggestions to implement an anti-ageing (according to the authors) nutritional geometry. Basically, based on the example of Okinawans, they get back to the 10% protein, 1:10 protein to carbs ratio as an ideal geometry.

 

Pls note, and this has been partly remarked by the authors, that to comply with such suggestions the diet must low fat, otherwise the 10% protein condition may be respected, but not the 1:10 P:C ratio.

 

The suggested dietary regimen is basically what the vegan doctors and cardiologists McDougall, Neil Barnard, Caldwell Esseltsyn, Joel Fuhrman, propose. A no fats or very low fat diet.

 

My geometry respect the 1st condition (10% P) whereas, due to the 45% content fat, cannot respect the second.

 

An important remark is that, to be perfectly complaint to the 1:10 P:C ratio, we should eat no fats at all. That makes the perfect geometry practically impossible.

 

Probably, a low fats approximation is what the authors suggest. I do not subscribe to such suggestion, since I see no reason to give up nuts and EVOO.

 

A 1:1:8 , or 1:2:7 P:F:C ratio would sure be more realistic, with a target of 1/8 to 1/7 P:C, which seems a reasonable approximation.