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My sister in law is currently following something called “The Blue Zone Diet” which is essentially a plant based diet with animal sources of protein restricted to one or two meals at most during the week. It is apparently a diet similar to the historical Okinawan diet. 

 

IIRC methionine is a sensor for mTor so mechanistically it makes sense. 

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The so-called Blue Zones are regions where there’s a high proportion of very old people, nonagenarians and centenarians. Is that really the truth about the Blue Zones?

 

What's The Truth About Blue Zones

 

The observation of individuals attaining remarkable ages, and their concentration into geographic sub-regions or ‘blue zones’, has generated considerable scientific interest. Proposed drivers of remarkable longevity include high vegetable intake, strong social connections, and genetic markers. Here, we reveal new predictors of remarkable longevity and ‘supercentenarian’ status. In the United States, supercentenarian status is predicted by the absence of vital registration. The state-specific introduction of birth certificates is associated with a 69-82% fall in the number of supercentenarian records. In Italy, which has more uniform vital registration, remarkable longevity is instead predicted by low per capita incomes and a short life expectancy. Finally, the designated ‘blue zones’ of Sardinia, Okinawa, and Ikaria corresponded to regions with low incomes, low literacy, high crime rate and short life expectancy relative to their national average. As such, relative poverty and short lifespan constitute unexpected predictors of centenarian and supercentenarian status, and support a primary role of fraud and error in generating remarkable human age records.

 

Supercentenarians and the oldest-old are concentrated into regions with no birth certificates and short lifespans

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Is there any suggestion at all that such a diet/lifestyle would reverse aging in any way? Obviously the gene therapy isn't happening anytime soon. 

Its a hard sell to suggest if I do X, Y and Z, I'll age more slowly, but I won't know its accomplishing anything until years have passed to the point I CLEARLY look/feel/examine younger than I should for my age. No one is going to the doctor to have their biological age measured, at least not yet. 

 

It would be a far more plausible scenario if we could follow such a diet/lifestyle sporadically in the way someone might currently be claiming to do a detox and come out of it actually looking and feeling younger. 

 

 

 

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IMHO, caloric restriction is the best shot you have at that along with mind-body based solutions such as meditation or yoga, etc., based on what I reviewed in the literature for my master's dissertation. The most applicable studies related to that are: 

 

1. Studies in primates, such as in the National Primate Research Center, that have found that 30% reduction in caloric intake significantly reduces the risk of insulin resistance, cardiovascular disease and cancer. Additionally, they found that it delayed hearing loss, sarcopenia and brain atrophy in subcortical regions. 

 

2. Studies from the Caloric Restriction Society (CRON). The individuals involved in CRON are very lean men and women that voluntarily restrict their calorie intake to approximately 1800 kcal daily for an average of 15 years, consuming approximately 30% less calories than an age, sex, and socioeconomically matched group of individuals consuming standard Western diet. Data from this study suggests that the metabolic factors involved in cardiovascular disease are remarkably low. Blood pressure was low even in the elderly, triglycerides are lowered, C-reactive protein was near undetectable, and insulin sensitivity as measured by HOMA2  was markedly increased. Further, their heart-rate variability was comparable to men and women 20 years younger. Interestingly, this reduction in caloric intake was not associated with IGF-1, which remained normal, unless protein intake was also significantly reduced. See Most et al. 2017 for an expanded elaboration on this. 

 

Based on my review, you do not want to lower IGF-1 at all, but rather instead focus on insulin sensitivity as the main thing for longevity purposes. Centenarians have much higher insulin sensitivity compared to non-centenarians. Interestingly, their offspring also have higher baseline insulin sensitivity. Metformin is right now being investigated in the TAME trials (Targeting Aging with Metformin). However, I am still skeptical regarding its use due to its effects on people that exercise. However, for sedentary people and especially people that eat a lot of carbohydrates, metformin is definitely something I could see being hugely beneficial. 

 

As for mind-body based solutions such as meditation or yoga - anything that strongly removes stress from your life is pretty profound, and has been shown to impact the aging process. I believe some of it may simply be through enhanced sleep and thus better regulated overall health. Sleep is paramount for health, as shown in detail by Matthew Walker in his research. His book published on this topic called Why We Sleep is certainly worth a perusal. 

 

From the abstract of a review entitled Can Meditation Slow Rate of Cellular Aging? Cognitive Stress, Mindfulness, and Telomeres?

 

Quote

Understanding the malleable determinants of cellular aging is critical to understanding human longevity. Telomeres may provide a pathway for exploring this question. Telomeres are the protective caps at the ends of chromosomes. The length of telomeres offers insight into mitotic cell and possibly organismal longevity. Telomere length has now been linked to chronic stress exposure and depression. This raises the question of mechanism: How might cellular aging be modulated by psychological functioning? We consider two psychological processes or states that are in opposition to one another-threat cognition and mindfulness-and their effects on cellular aging. Psychological stress cognitions, particularly appraisals of threat and ruminative thoughts, can lead to prolonged states of reactivity. In contrast, mindfulness meditation techniques appear to shift cognitive appraisals from threat to challenge, decrease ruminative thought, and reduce stress arousal. Mindfulness may also directly increase positive arousal states. We review data linking telomere length to cognitive stress and stress arousal and present new data linking cognitive appraisal to telomere length. Given the pattern of associations revealed so far, we propose that some forms of meditation may have salutary effects on telomere length by reducing cognitive stress and stress arousal and increasing positive states of mind and hormonal factors that may promote telomere maintenance. Aspects of this model are currently being tested in ongoing trials of mindfulness meditation.

 

One has to take into account that - if we go by the concept of hallmarks of aging as expressed by Lopez-Otin et al in Cell 2013, telomere shortening is only one part of cellular aging, the remaining being: genomic instability, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication.

 

Anyway, hope this helps and gives some food for thought :) 

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1 minute ago, Something Anonymous said:

So good to hear from you Kass. This is Brandon. 

 

Hey man! All well? :) Just finished up my master's dissertation and only six months left of medschool so super busy. Much love. 

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2 hours ago, kassem23 said:

 

Hey man! All well? :) Just finished up my master's dissertation and only six months left of medschool so super busy. Much love. 

 

Back at you brother. Congrats on your dissertation! I recall when you first entered med school. That’s just great and I am happy for you. Have you decided on a specialty?

 

All is well on my end. My career is going well - just earned a promotion into upper management at my company and my two boys are deeply involved in sports and school. 

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Welcome back, Kassem. Good to have you around as always.

 

Caloric restriction has always been interesting to me, but it's not compatible with an active lifestyle. Have you found any interesting research in the area of calorie restriction mimetics?

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6 hours ago, Something Anonymous said:

Back at you brother. Congrats on your dissertation! I recall when you first entered med school. That’s just great and I am happy for you. Have you decided on a specialty?

 

All is well on my end. My career is going well - just earned a promotion into upper management at my company and my two boys are deeply involved in sports and school. 

 

Thanks brother. Thinking family medicine and making my own practice so I can help with optimisation and add some extra protocols without issue. Also like the idea of running my own business and not being tied down to a hospital. We'll see though. :) 

 

Congratulations on the promotion, that sounds great. Amazing on the kids, how old are they now? And how old were you when you had them? My girlfriend keeps pestering me about kids... 😅My elder sister has a 2 year old we hang out with every now and then and it's really great fun.

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5 hours ago, Construct said:

Welcome back, Kassem. Good to have you around as always.

 

Caloric restriction has always been interesting to me, but it's not compatible with an active lifestyle. Have you found any interesting research in the area of calorie restriction mimetics?

 

Thanks man. Hope you're doing well! 

 

True on the restricting calories if you have an active lifestyle. What you could do instead is to do time-restricted eating. Fasting by itself has hugely beneficial effects, and I'd say its the closest you get at mimicking the positive effects of calorie restriction. Keep in mind that when you do fast like 24-72 hours every now and then, you cause manifold beneficial changes biologically. You won't have reduced gains or anything like that as long as you continue to eat properly during the rest of the time. Fasting 24 hours once a week or once ever 2 weeks can be great. If you're the type that does weight/resistance training (most on here seem to), if you don't want to lose dem gainz, be sure to workout fasted. This is important to maintain muscle mass during the fast. 

 

Just some of the good things that happens with the glycogen depletion is inhibition of mTOR, activation of AMPK, the significant reduction of insulin and glucose (due to entering ketosis) leading to autophagy and inhibition of senescent cells. 

 

As for actual compounds, outside of metformin and berberine, I'm afraid not. 

Edited by kassem23

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It's all in your head...

 

Researchers are finding that your mental patterns could be harming your telomeres — essential parts of the cell’s DNA — and affecting your life and health. Nobel Prize-winning scientist Elizabeth Blackburn and health psychologist Elissa Epel explain.

 

Full Article

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