Inflammation not telomeres key to successful aging

[Mike41]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634197/
 

this study is 4 years ago not sure if it was posted or not. IAC inflammation was a more important factor than telomere length in predicting longevity. 

[Saul]

Not a big surprise.

  --  Saul

 

[Mechanism]

That's a great study Mike.  I was going to say yes, consistent with a study that Rhonda Patrick of Foundmyfitness.com has cited several times.  Then I clicked on the link handily provided, and found it is the same 2015 study.  Just as true now as then - with evidence for both causality and reverse-causality, and almost certainly both operating.

Thank you Mike!

Edited August 19, 2020 by Mechanism

[Clinton]

Good post Mike, and I've seen that paper before.

I also believe that the two (maximizing telomere length and minimizing inflammation) are not mutually exclusive and rather optimizing one seems to compliment the other.   I think that the diet that which maximizes telomere length (or telomere recovery) is also highly anti-inflammatory.  Optimal nutrition, high fiber (whole grains, legumes, vegetables, fruits), omega 3's, proper sleep, etc. etc..

I've looked at this jigsaw puzzle (of aging) from many angles (free radicals, mitochondria, telomeres, inflammation, micronutrients, etc.) and which intervention(s) available to us in the present seem to be most effective for each separate piece of the puzzle; and it seems to me that the majority of the (natural) interventions seem to be aligned/congruent.  

 

[TomBAvoider]

If inflammation seems to be the problem, then perhaps anti-inflammatory agents might be useful. There is some speculation that the good effect (insofar as it is good!) of statins might be through anti-inflammatory properties. On the other hand, some anti-inflammatory agents - like aspirin - have largely been a bust in the anti-aging context. Exercise is pro-inflammatory, but the reaction to it, the recovery or adaptation in a hormetic process ends up net anti-inflammatory in effect.  

[Mechanism]

Luigi Ferrucci is NIA's scientific director.  Much of his work has focused on the relationship between inflammation and frailty.  He wrote a very nice review of the subject in 2017: "Aging, Inflammation and the Environment" (1).  It does a great job going into the underlying basic science.  A more clinical focus ( and easier read for the casual reader less comfortable going into mechanisms and more interested in applications) was a collaboration published in Nature Medicine (2).  You will recognize many of the authors here such as Nir Barzilai ( of his TAME study [re: metformin] and the "Age Later" book), Judith Campisi for her pioneering work on senescence, Eric Verdin from the Buck, etc.  It was very well written and has sections focusing for example on physical activity, environmental toxins, nutrition, the microbiome, etc.

I would be remiss not to mention one other review, specifically focusing on CR and Senoinflammation (3) - recall that much of inflammation is SASP byproduct from senescent cell ( along with primarily non-specific immunological activation with some hotspots such as in association with visceral fat, endogenous and exogenous sources of AGE / glycosylation, etc.).   Lots of focus on the anti-senoinflammatory effect of CR, as well as a few CR-mimetics. 

Lots of others, but these are my current favorites.  

I mentioned the problem of reverse-causality in the previous post ( association is not causation, and aging can cause inflammation rather than just vice versa; certainly some degree of both is happening and these relationships are still being elucidated) and another issue was brought up above is regarding the use of antioxidants - which are mostly not helpful supplementing except to replete a deficiency or address specific stress situations and have been found to be counter-productive for most "natural" models of aging; indeed the oxidative theory of aging has been undermined over the years by various evidences but that is a whole other story).  There was a beautiful recent publication in Harvard Magazine ( excerpt from a book, and regretfully not without a quick citation though I'm sure it is not hard to pick up the individual studies, some of which we have read and discussed here previously - the vitamin C, E, and A studies are absolute classics, I am sure we are all familiar with them), which looked at this from the perspective of exercise.  I will quote this eloquent short passage here (source: https://www.harvardmagazine.com/2020/09/features-active-grandparenting

"The problem is that dozens of studies have found that taking antioxidant pills is no substitute for physical activity to fight senescence. Three or four studies reported a modest benefit, but the rest found that antioxidants provided no benefit or even increased the risk of dying. To add insult to injury, additional studies suggest antioxidants may sometimes do more harm than good when combined with exercise. This head-turning conclusion followed from a groundbreaking 2009 experiment by Michael Ristow, a researcher in Zurich who studies aging and metabolism. His team asked 40 healthy young males with varied fitness levels to undergo four weeks of supervised exercise. Half the participants were given large doses of vitamins C and E, the other half received a placebo. Muscle biopsies taken before and after their exercise bouts showed that, as expected, physical activity induced plenty of oxidative stress, but those who took antioxidants incurred more oxidative damage because their bodies produced much lower levels of their own antioxidants. The antioxidant pills apparently suppressed the body’s normal anti-stress response, probably because oxidative damage from exercise itself is needed to trigger the body’s health-promoting antioxidative defense mechanisms."

 

(1) Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2018). Aging, inflammation and the environment. Experimental gerontology, 105, 10–18.  https://doi.org/10.1016/j.exger.2017.12.015

(2) Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., Miller, A. H., Mantovani, A., Weyand, C. M., Barzilai, N., Goronzy, J. J., Rando, T. A., Effros, R. B., Lucia, A., Kleinstreuer, N., & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature medicine, 25(12), 1822–1832. https://doi.org/10.1038/s41591-019-0675-0

(3) Kim, D. H., Bang, E., Jung, H. J., Noh, S. G., Yu, B. P., Choi, Y. J., & Chung, H. Y. (2020). Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept. Nutrients, 12(2), 422.  https://doi.org/10.3390/nu12020422

Edited August 20, 2020 by Mechanism

[Mike41]

4 hours ago, Mechanism said:

Luigi Ferrucci is NIA's scientific director.  Much of his work has focused on the relationship between inflammation and frailty.  He wrote a very nice review of the subject in 2017: "Aging, Inflammation and the Environment" (1).  It does a great job going into the underlying basic science.  A more clinical focus ( and easier read for the casual reader less comfortable going into mechanisms and more interested in applications) was a collaboration published in Nature Medicine (2).  You will recognize many of the authors here such as Nir Barzilai ( of his TAME study [re: metformin] and the "Age Later" book), Judith Campisi for her pioneering work on senescence, Eric Verdin from the Buck, etc.  It was very well written and has sections focusing for example on physical activity, environmental toxins, nutrition, the microbiome, etc.

I would be remiss not to mention one other review, specifically focusing on CR and Senoinflammation (3) - recall that much of inflammation is SASP byproduct from senescent cell ( along with primarily non-specific immunological activation with some hotspots such as in association with visceral fat, endogenous and exogenous sources of AGE / glycosylation, etc.).   Lots of focus on the anti-senoinflammatory effect of CR, as well as a few CR-mimetics. 

Lots of others, but these are my current favorites.  

I mentioned the problem of reverse-causality in the previous post ( association is not causation, and aging can cause inflammation rather than just vice versa; certainly some degree of both is happening and these relationships are still being elucidated) and another issue was brought up above is regarding the use of antioxidants - which are mostly not helpful supplementing except to replete a deficiency or address specific stress situations and have been found to be counter-productive for most "natural" models of aging; indeed the oxidative theory of aging has been undermined over the years by various evidences but that is a whole other story).  There was a beautiful recent publication in Harvard Magazine ( excerpt from a book, and regretfully not without a quick citation though I'm sure it is not hard to pick up the individual studies, some of which we have read and discussed here previously - the vitamin C, E, and A studies are absolute classics, I am sure we are all familiar with them), which looked at this from the perspective of exercise.  I will quote this eloquent short passage here (source: https://www.harvardmagazine.com/2020/09/features-active-grandparenting

"The problem is that dozens of studies have found that taking antioxidant pills is no substitute for physical activity to fight senescence. Three or four studies reported a modest benefit, but the rest found that antioxidants provided no benefit or even increased the risk of dying. To add insult to injury, additional studies suggest antioxidants may sometimes do more harm than good when combined with exercise. This head-turning conclusion followed from a groundbreaking 2009 experiment by Michael Ristow, a researcher in Zurich who studies aging and metabolism. His team asked 40 healthy young males with varied fitness levels to undergo four weeks of supervised exercise. Half the participants were given large doses of vitamins C and E, the other half received a placebo. Muscle biopsies taken before and after their exercise bouts showed that, as expected, physical activity induced plenty of oxidative stress, but those who took antioxidants incurred more oxidative damage because their bodies produced much lower levels of their own antioxidants. The antioxidant pills apparently suppressed the body’s normal anti-stress response, probably because oxidative damage from exercise itself is needed to trigger the body’s health-promoting antioxidative defense mechanisms."

 

(1) Bektas, A., Schurman, S. H., Sen, R., & Ferrucci, L. (2018). Aging, inflammation and the environment. Experimental gerontology, 105, 10–18.  https://doi.org/10.1016/j.exger.2017.12.015

(2) Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., Miller, A. H., Mantovani, A., Weyand, C. M., Barzilai, N., Goronzy, J. J., Rando, T. A., Effros, R. B., Lucia, A., Kleinstreuer, N., & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature medicine, 25(12), 1822–1832. https://doi.org/10.1038/s41591-019-0675-0

(3) Kim, D. H., Bang, E., Jung, H. J., Noh, S. G., Yu, B. P., Choi, Y. J., & Chung, H. Y. (2020). Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept. Nutrients, 12(2), 422.  https://doi.org/10.3390/nu12020422

Thanks Mechanism a very important point made. Supplements are very dicey to say the least even some of the most benign ones! Yes they are so tempting. We humans are always looking for the magic fix. For the most part, diseases aside like massive infections, heart disease etc., sticking to a sensible diet, moderate exercise, not smoking, maintaining proper muscle to fat ratio, stress control, socialization etc. is truly the best we got. All these pills are generally without long term research. Too many unknowns.

[Mechanism]

Right.  The most sensible guide to supplements I have read - from a philosophical standpoint - was from none other than MR.  I don't necessarily follow or endorse his protocol per se - but rather the philosophy behind it, which closely parallels my own. 

In his thread on the subject ( https://www.longecity.org/forum/stacks/stack/122-michaels-tiered-supplement/ ) he quoted Oakman, and I will credit Michael for crediting him:

"This is put very well in Oakman's "pothole theory" of supplementation"

----> from Oakman "If you don't have a 'hole' in your metabolism, meaning a diminished ability to produce something due to age or malfunction, or lacking it altogether, supplementation isn't unlikely to help. Plus, you only need enough to fill the 'hole,' not more (i.e., a "bump" is as bad as a "hole")."

Mechanism again:

Precision, personalized medicine recognizes everybody is different, so in my book there is no one supplement regimen fit for all.  But whether you take lots of supplements or just vitamin D or vitamin B-12, remember Oakman's wisdom.***

*** [ Mechanism footnote]: Every great rule has exceptions; there is something to the difference between sufficiency and optimal levels... it is a matter of semantics as well as practice how high a dose is needed to fill the hole.... it may be more than the RDA depending on the person, condition, circumstances, etc.  Though the ultimate role for geroprotectors are still being worked out, it would be prudent to optimize the dietary foundation of good nutrition through a moderated calorie, minimally processed and refined diverse whole foods based diet first, only then turning to supplements if and as required and desired beyond those limits.  

Edited August 20, 2020 by Mechanism

[Clinton]

Great thread ... thanks much to all above posters 

[Ron Put]

"A study of thousands found that the average twenty-first-century woman in the United States aged 18 to 40 walks 5,756 steps a day (about 2-3 miles), but this number declines precipitously with age, and by the time they are in their 70s, American women take roughly half as many steps. While Americans are half as active in their 70s as in their 40s, Hadza women walk twice as much per day as Americans with only modest declines as they age."

The above, from the article cited by Mechanism, was a bit surprising to me.  Hunter-gatherers walk approximately less than 12,000 steps on average per day?  I expected it to be significantly more.

[Mike41]

Ron Putt said:

The above, from the article cited by Mechanism, was a bit surprising to me.  Hunter-gatherers walk approximately less than 12,000 steps on average per day?  I expected it to be significantly more
 

Im not surprised by that. Conservation of energy matters wrt  natural selection. Do enough to take care of basic necessities and conserve body fat for those times Of scarcity.