Thursday, February 9, 2023
Mitochondrial Health

Protein: the Key to Longevity



00:00 INTRO
02:47 DIETARY RESTRICTION
06:03 MTOR
09:59 AGING
11:52 CR & MTOR
13:13 AMINO ACIDS
15:56 IGF-1
17:34 GCN2
18:36 FGF-21
20:36 AMINO ACIDS
26:57 2014 Paper
29:16 2016 Paper
30:27 2020 Meta-analysis
31:26 OTHER CONCERNS
33:42 SUMMARY

JOIN OUR COMMUNITY:
Reddit ▶ https://www.reddit.com/r/TheLongLived/

FOR GENETIC ANALYSIS & CONSULTATIONS:
Website ▶ https://www.leoandlongevity.com

TO READ MY ARTICLES:
Blog ▶ https://www.leoandlongevity.com/blog

TO FOLLOW ME ON SOCIAL MEDIA:
Instagram ▶ https://www.instagram.com/leoandlongevity
Twitter ▶ https://www.twitter.com/leoandlongevity
Facebook ▶ https://www.facebook.com/LeoLongevity

Gorilla Mind 10% Discount: LEO
Affiliate Link: https://gorillamind.com/?rfsn=5750379.0e4babc

source

Similar Posts

44 thoughts on “Protein: the Key to Longevity
  1. Citations:
    – Lee, C., & Longo, V. (2016). Dietary restriction with and without caloric restriction for healthy aging. F1000Research, 5.
    – Cornaro, L. (1905). The Art of Living Long: A New and Improved English Version of the Treatise. WF Butler.
    – Osborne, T. B., Mendel, L. B., & Ferry, E. L. (1917). The effect of retardation of growth upon the breeding period and duration of life of rats. Science, 45(1160), 294-295.
    – Mattison, J. A., Colman, R. J., Beasley, T. M., Allison, D. B., Kemnitz, J. W., Roth, G. S., … & Anderson, R. M. (2017). Caloric restriction improves health and survival of rhesus monkeys. Nature communications, 8(1), 1-12.
    – National Academies of Medicine. Dietary reference intakes for energy C, fiber, fat, fatty acids, cholesterol, protein, and amino acids (macronutrients). Available from: http://nationalacademies.org/ hmd/w/media/Files/Activity%20Files/Nutrition/DRI-Tables/8_ Macronutrient%20Summary.pdf?laZen.
    – McCay, C. M., Bing, F. C., & Dilley, W. E. (1928). Factor H in the nutrition of trout. Science, 67(1731), 249-250.
    – Slonaker, J. R. (1931). THE EFFECT OF DIFFERENT PER CENTS OF PROTEIN IN THE DIET: I. Growth. American Journal of Physiology-Legacy Content, 96(3), 547-556.
    – Davis, T. A., Bales, C. W., & Beauchene, R. E. (1983). Differential effects of dietary caloric and protein restriction in the aging rat. Experimental gerontology, 18(6), 427-435.
    -Mair, W., Piper, M. D. W., & Partridge, L. (2005). Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS biology, 3(7), e223.
    – Lee, K. P., Simpson, S. J., Clissold, F. J., Brooks, R., Ballard, J. W. O., Taylor, P. W., … & Raubenheimer, D. (2008). Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proceedings of the National Academy of Sciences, 105(7), 2498-2503.
    – Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., … & Simpson, S. J. (2014). The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell metabolism, 19(3), 418-430.
    – Sanz, A., Caro, P., & Barja, G. (2004). Protein restriction without strong caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat liver. Journal of bioenergetics and biomembranes, 36(6), 545-552.
    – Ayala, V., Naudí, A., Sanz, A., Caro, P., Portero-Otin, M., Barja, G., & Pamplona, R. (2007). Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62(4), 352-360.
    – Sanz, A., Caro, P., Sanchez, J. G., & Barja, G. (2006). Effect of lipid restriction on mitochondrial free radical production and oxidative DNA damage. Annals of the New York Academy of Sciences, 1067(1), 200-209.
    – Sanz, A., Gomez, J., Caro, P., & Barja, G. (2006). Carbohydrate restriction does not change mitochondrial free radical generation and oxidative DNA damage. Journal of Bioenergetics and Biomembranes, 38(5), 327-333.
    – Papadopoli, D., Boulay, K., Kazak, L., Pollak, M., Mallette, F. A., Topisirovic, I., & Hulea, L. (2019). mTOR as a central regulator of lifespan and aging. F1000Research, 8.
    – Vezina, C., Kudelski, A., & Sehgal, S. N. (1975). Rapamycin (AY-22, 989), a new antifungal antibiotic I. taxonomy of the producing streptomycete and isolation of the active principle. The Journal of antibiotics, 28(10), 721-726.
    – Saxton, R. A., & Sabatini, D. M. (2017). mTOR signaling in growth, metabolism, and disease. Cell, 168(6), 960-976.
    – Fabrizio, P., Pozza, F., Pletcher, S. D., Gendron, C. M., & Longo, V. D. (2001). Regulation of longevity and stress resistance by Sch9 in yeast. science, 292(5515), 288-290.
    – Oh, J., Lee, Y. D., & Wagers, A. J. (2014). Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nature medicine, 20(8), 870-880.
    – Takayama, K., Kawakami, Y., Lavasani, M., Mu, X., Cummins, J. H., Yurube, T., … & Huard, J. (2017). mTOR signaling plays a critical role in the defects observed in muscle‐derived stem/progenitor cells isolated from a murine model of accelerated aging. Journal of Orthopaedic Research, 35(7), 1375-1382.
    – Dhillon, R. S., & Denu, J. M. (2017). Using comparative biology to understand how aging affects mitochondrial metabolism. Molecular and cellular endocrinology, 455, 54-61.
    – Zhang, H., Menzies, K. J., & Auwerx, J. (2018). The role of mitochondria in stem cell fate and aging. Development, 145(8), dev143420.
    – McGuire, P. J. (2019). Mitochondrial dysfunction and the aging immune system. Biology, 8(2), 26.
    – Bartolomé, A., García-Aguilar, A., Asahara, S. I., Kido, Y., Guillén, C., Pajvani, U. B., & Benito, M. (2017). MTORC1 regulates both general autophagy and mitophagy induction after oxidative phosphorylation uncoupling. Molecular and Cellular Biology, 37(23), e00441-17.
    – Koga, H., Kaushik, S., & Cuervo, A. M. (2011). Protein homeostasis and aging: The importance of exquisite quality control. Ageing research reviews, 10(2), 205-215.
    – Powers, E. T., Morimoto, R. I., Dillin, A., Kelly, J. W., & Balch, W. E. (2009). Biological and chemical approaches to diseases of proteostasis deficiency. Annual review of biochemistry, 78, 959-991.
    – Taylor, R. C. (2016). Aging and the UPR (ER). Brain research, 1648, 588-593.
    – Pfaffenbach, K. T., Nivala, A. M., Reese, L., Ellis, F., Wang, D., Wei, Y., & Pagliassotti, M. J. (2010). Rapamycin inhibits postprandial-mediated X-box-binding protein-1 splicing in rat liver. The Journal of nutrition, 140(5), 879-884.
    -Walter, P., & Ron, D. (2011). The unfolded protein response: from stress pathway to homeostatic regulation. science, 334(6059), 1081-1086.
    – Guan, B. J., Krokowski, D., Majumder, M., Schmotzer, C. L., Kimball, S. R., Merrick, W. C., … & Hatzoglou, M. (2014). Translational control during endoplasmic reticulum stress beyond phosphorylation of the translation initiation factor eIF2α. Journal of Biological Chemistry, 289(18), 12593-12611.
    – Gandin, V., Masvidal, L., Cargnello, M., Gyenis, L., McLaughlan, S., Cai, Y., … & Topisirovic, I. (2016). mTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nature communications, 7(1), 1-15.
    — Roux, P. P., & Topisirovic, I. (2018). Signaling pathways involved in the regulation of mRNA translation. Molecular and cellular biology, 38(12), e00070-18.
    – Lindqvist, L. M., Tandoc, K., Topisirovic, I., & Furic, L. (2018). Cross-talk between protein synthesis, energy metabolism and autophagy in cancer. Current opinion in genetics & development, 48, 104-111.
    – Zhao, J., Zhai, B., Gygi, S. P., & Goldberg, A. L. (2015). mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy. Proceedings of the National Academy of Sciences, 112(52), 15790-15797.
    – Campisi, J. (2013). Aging, cellular senescence, and cancer. Annual review of physiology, 75, 685-705.
    – Narita, M., Young, A. R., Arakawa, S., Samarajiwa, S. A., Nakashima, T., Yoshida, S., … & Narita, M. (2011). Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science, 332(6032), 966-970.
    – Carroll, B., Nelson, G., Rabanal-Ruiz, Y., Kucheryavenko, O., Dunhill-Turner, N. A., Chesterman, C. C., … & Korolchuk, V. I. (2017). Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing. Journal of Cell Biology, 216(7), 1949-1957.
    – Herranz, N., Gallage, S., Mellone, M., Wuestefeld, T., Klotz, S., Hanley, C. J., … & Gil, J. (2015). mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nature cell biology, 17(9), 1205-1217.
    – Laberge, R. M., Sun, Y. U., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., … & Campisi, J. (2015). MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nature cell biology, 17(8), 1049-1061.
    – Kolesnichenko, M., Hong, L., Liao, R., Vogt, P. K., & Sun, P. (2012). Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence. Cell cycle, 11(12), 2391-2401.
    – Anderson, R. M., Le Couteur, D. G., & de Cabo, R. (2018). Caloric restriction research: new perspectives on the biology of aging. The Journals of Gerontology: Series A, 73(1), 1-3.
    – Lamming, D. W., Cummings, N. E., Rastelli, A. L., Gao, F., Cava, E., Bertozzi, B., … & Fontana, L. (2015). Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model. Oncotarget, 6(31), 31233.
    – Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004). Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Current Biology, 14(10), 885-890.
    – Hansen, M., Taubert, S., Crawford, D., Libina, N., Lee, S. J., & Kenyon, C. (2007). Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging cell, 6(1), 95-110.
    – Kaeberlein, M., Powers III, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., … & Kennedy, B. K. (2005). Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science, 310(5751), 1193-1196.

  2. I think the biggest problem is that people mix meat with rice or their food in general. resulting in long-term health problems. Therefore, these studies and assumptions are not meaningful for me. I can only explain it to myself with disturbed protein digestion, which, as mentioned, is caused over time by a mixed diet. Therefore, in these cases, a low-protein diet might be better.

  3. Complete BS studies ALL.are reductionist in nature ! Follow the money on the studies. The reality MOST people over 50 consume to little animal protein especially in the optimal pulsing range ! Look at the epdemic of muscle wasting in senior population! Seniors literally waste away ! The extended life pathways are probably the results of ketogenesis. You can get to this 2 ways starve the body and under eat or eat a species appropriate diet ! EVERY iso-carbon nitrogen test on ancient humans as shown us to be " hyper carnivores " . The main problems with humans , sickness and longevity? We are NOT eating a species appropriate diet ! ALL plant matter is toxic it was back up food our ancestors would have avoided ! Look up professor Bart Kay ! One of the leading scientists on Human nutrition

  4. doesn't life age you? These guys are all looking for the fountain of youth without realizing there isn't one. People will never live past 120. It states that directly in the Bible that that is the maximum, and its been proven over and over with the longest lived people. Just keep your stress down, sleep well, and exercise. Chasing this nonsense is like a dog chasing its own tail.

  5. Leo, for me what missing is presentation of definition of the "low protein" and "high protein" diet in terms of grams per kg, or % of total calories. There was some touch in the begining of the video, but not really fully explained.

  6. So what do we do about the fact that our human body, converts everything we eat into animal protein and fat, that it distributes all over our entire body to eat later for our entire life?

  7. Here is wisdom.
    Until you know how to separate the mind from the heart is the moment you become "saved".
    You are a walking contradiction and you dont even know it.
    The battle of flesh vs the soul is in every single individual in history.
    Yet, none of this is possible without an grand design. That means there is a grand designer.
    Until you actually know, you actually know nothing.
    Yet, knowing is not a choice you can make. You can not choose to know.
    You are chosen and it is verily verily set in stone. That stone is the head cornerstone and until your roots are embedded in Him, you are just a walking contradiction aimlessly wondering in a long inner monologue as you call other people crazy yet it is you who is decieved.
    Only GOD can answer all questions.
    Have you ever asked yourself why YOU exist at all?

  8. Thanks for clarifying such a complex and controversial subject…high protein vs low protein etc. I’m wondering if jello is a new anti aging food with its glycine content 😂 keep up the good research 🔬

  9. Interesting.

    Lee Labrada always advocated a higher protein and less carbs diet and he's always looked amazing for his age.

    I also know of a friend of Vince Girondha that was an indian farmhand, who only ate meat( and every part of the animal he could) and his skin and muscle tone were always amazing throughout his life.

    He never ate any fruit, even when the kids would offer him some.

    He'd just shake his head and say, "you crazy kids."

    There's another surgeon guy on youtube, and he has been a rugby player and on the meat diet for decades and is 42 and looks at least a decade younger, and is in tremendous muscular shape, with great definition.

    Something Caffee M.D. I think his channel is called.

    Oh, btw, the indian guy lived in perfect health and died at 118 years old.

    Another doctor recommends mostly protein for the diet (grassfed prefferably) is able to cure autism if caught early enough while the child is still young.

    She was one of the first proponents in the medical community that advocated that most of your immune system is in your gut and it needs to be healed.

    They used to make fun of her and call her a quack in the medical field, until the findings are showing it to be true once they started investigating this for themselves and actually following the protocols and healing people/restoring people's health.

    She says that when all else fails to heal the gut, she puts them on a diet of meat.

    I can't remember her name rn, but when I find it, I'll put her name in this post.

    She has a whole talk explaining these things right on youtube, and how plants are meant as cleansers, not something to thrive off of and even has seen cases were vegetarians come to her w/ cancer and she puts them on meat and protein to fix them.

  10. So how would one combine eating for longevity and recreational bodybuilding? Cycling through cutting, bulking and maintenance? Intermittent fasting? 24h+ fast every few weeks?

  11. So we are here for a good time not a (longer) time. Kinda interesting to see the balance. If you havent already covered it yet, how does metabolism affect life expectancy?

  12. So idealistically you should not eat many carbs, because that is bad. You should not eat protein, because that ages you. I am sure it is possible to find something negative about fat as well. So then we have managed to exclude all three macros. We WILL die some day, that is the only thing that is certain. So … please try to have as much fun as possible on your way to that day.

  13. 33:15 MPMD Derek's nitric preworkout has more than gram of sodium nitrate per serving. Would it concern you? It's much much more than the amount contained in processed meats. What are your thoughts on beet root?

  14. Why then do we see significant deterioration of health and accelerated ageing in prolonged vegan diets (including those who are "doing it right")? From what you have said, theoretically we should see the opposite?

  15. Hello Leo.
    Thank you for the continuation of this series.
    I would like you to consider a topic to continue the diet series.
    If you would be able to explain the effects of essential fats in the brain, and body. As well as possibly some of the common sources to obtain these fats in our diets.

  16. Hey Leo,

    very interesting deep dive into this topic. Yet, since you seem to draw quite definite conclusions from your research (and a lot of your listeners seem to do the same), I feel the need to put it into perspective just a little bit by copy&pasting a former comment of mine on one of your previous videos on protein. Here you go:

    Hey Leo,

    first and foremost since I didn´t comment here yet (or anywhere else for that matter): Thank you for your great work – I´ve already learned quite a lot through your channel in multiple fascets of life.

    Since I hold a Bachelors degree in Nutritional Sciences and a Masters in Sports Nutrition and actually wrote my thesis about the connection between nutrition (particularly regular protein/leucine-rich feedings like it is practiced among strength athletes), the regulation of the mTOR-pathway and the molecular and cellular causes of aging, I feel like clarifying a few things.

    1. As you probably know, the Physiology of aging beyond small model-organisms like yeast and c.elegans is quite controversial and mostly based on theories yet(Mitochondrial Dysfunktion/"Vicious cycle" of ROS, cellular senescence and its inflammatory phenotype, Dysregulation of autophagie and mRNA translation and a consequent buildup of "protein waste" within the cytosol of the cell tc.), lacking a clear causial relationship in humans while even on these mechanistic levels there are still many open questions.

    2. The data showing a connection between lifespan and mTOR is quite evident with an inverse relationship, yes, yet only in models with completely dysregulated mTOR (so either knockout animals for example or, more interesting here, genetically chronically hyperactive mTOR, constantly promoting protein translation). The second case is, even in theory, not comparable to protein feeding since under physiological conditions mTOR actually has a refractory time between around 2-5 hours (which is also why bodybuilders tend to have protein with these lags rather than having leucine infusions). Meaning that mTOR has to go down first in order to be stimulated again and also can´t be stimulated to this extreme through feeding in comparison to these mTOR-hyperactive model-designs.

    So yes, in theory it can still be the case that high (or rather high-regular) protein feedings can shorten lifespan but there is no clear evidence to absolutely draw that conclusion yet, at least from what I´ve seen.

    3. When you talk about replicative senescence, keep in mind that this isn´t relevant for all cell types but rather just all of them that still go through hyperplasia after embryonic and fetal development (I think it was even derived through the so called Hayflick-limit in fibroblasts specifically, even though especially also neuronal cell types seem to be quite sensitive to this too, so it is an interesting theory regarding neurodegeneration). Since the leucine-mTOR axis is mostly relevant to muscle cells, it would be questionable if regular protein really would promote that phenotype and therefore aging (if this theory even holds true)

    4. What I see as the most likely connection is with the inhibition of autophagy as well as more translation errors through even just slightly higher protein synthesis rates leading to more "protein waste" within the cytosol from both sites which thereby also promotes an inflammatory phenotype of the cell but even that I would still be sceptic about at this point.

    5. Nutritional science (or rather the actual branch of "food science") is shit. On one hand, you mostly rely on observational research and if you actually have RCTs they are quite worthless since you have a shitton of more possible errors, biases and confounding variables as in pharmacological or even supplement research for example that you can never attest for as well as the question "with what did people replace food group x and isn´t this probably the reason for the observed effects". After being into this research for an eternity now, I´m getting more and more sceptic about its value tbh

    These are just my two cents and I would hope this doesn´t come off cunty but rather sparks a discussion about this fascinating connection of lifestyle and longevity again 🙂

    P.S. I´m actually from germany so I already apologize if my english failed me at some points.

    Especially point 5 I would want to emphasize in this context, regarding the studies you presented. You´ve kinda said it yourself at the end that the associations could be due to many other factors since people with higher protein contents within their diet definietly share other, probably harmful lifestyle-measures that can´t all be methodologically and statistically be accounted for.

    I don´t want to destroy your theory at all. i mean, I´ve asked myself the same question a few years back too and dove into the whole research but I think it´s definietly to early to draw the definite conclusion that protein ages and it should be communicated this way to the audience.

    All the best to you

  17. It comes down to quality of life vs length of life. Imma go for the middle by eating the recommended amount of protein while trying to build muscles while also fasting 3 days a month every month.

Leave a Reply

Your email address will not be published.