How to Suppress the Aging Enzyme TOR

Prevent Cancer From Going on TOR
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Over the last decade, more than 5,000 papers have been published about TOR, an engine-of-aging enzyme inhibited by the drug rapamycin. (What is TOR? Check out my videos Why Do We Age? and Caloric Restriction vs. Animal Protein Restriction.) Rapamycin has been used experimentally to extend lifespan, but is already in use clinically to prevent the rejection of kidney transplants. Patients who received rapamycin due to renal transplantation had a peculiar “side effect,” a decrease in cancer incidence. In a set of 15 patients who had biopsy proven Kaposi’s sarcoma (a cancer that often affects the skin), all cutaneous sarcoma lesions disappeared in all patients within three months after starting rapamycin therapy.

TOR functions as a master regulator of cellular growth and proliferation. For example, TOR is upregulated in nearly 100% of advanced human prostate cancers (See Prevent Cancer From Going on TOR). So, reductions in cancerous lesions after rapamycin therapy make sense. TOR may also be why dairy consumption has been found to be a major dietary risk factor for prostate cancer. We used to think it was just the hormones in milk, but maybe prostate cancer initiation and progression is also promoted by cow’s milk stimulation of TOR.

Our understanding of mammalian milk has changed from a simple food to a “species-specific endocrine signaling system,” which activates TOR, promoting cell growth and proliferation and suppressing our body’s internal housecleaning mechanisms. Normally, milk-mediated TOR stimulation is restricted only to infancy where we really need that constant signal to our cells to grow and divide. So, from an evolutionary perspective, “the persistent ‘abuse’ of the growth-promoting signaling system of cow’s milk by drinking milk over our entire life span may maintain the most important hallmark of cancer biology, sustained proliferative signaling.”

TOR appears to play a role in breast cancer, too. Higher TOR expression has been noted in breast cancer tumors, associated with more aggressive disease, and lower survival rate among breast cancer patients. Altered TOR expression could explain why women hospitalized for anorexia may end up with only half the risk of breast cancer. Severe caloric restriction in humans may confer protection from invasive breast cancer by suppressing TOR activation.

We don’t have to starve ourselves to suppress TOR; just reducing animal protein intake can attenuate overall TOR activity. Moreover, diets emphasizing plants, especially cruciferous vegetables, decrease TOR activation from animal proteins while providing natural plant-derived inhibitors of TOR found in broccoli, green tea, soy, turmeric, and grapes, along with other fruits and vegetables such as onions, strawberries, blueberries, mangoes and the skin of cucumbers.

The downregulation of TOR may be one reason why plant-based diets in general are associated with lower risk for many cancers. “Are we finally on the threshold of being able to fundamentally alter human aging and age-related disease?” ask researchers in the journal Nature. Only time will tell, but if the pace and direction of recent progress are any indication, the next 5,000 studies on TOR should prove very interesting indeed.

More on dairy and prostate cancer in Prostate Cancer and Organic Milk vs. Almond Milk.

This story continues in my video: Saving Lives By Treating Acne With Diet.

-Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live year-in-review presentations Uprooting the Leading Causes of DeathMore Than an Apple a DayFrom Table to Able, and Food as Medicine.

Image Credit: Grempz / Flickr

  • Thea

    Dr. Greger: I almost missed the funny. Then it hit me what you were really saying here:
    “Only time will tell, but if the pace and direction of recent progress are any indication, the next 5,000 studies on TOR should prove very interesting indeed.” ;-)
    .
    Happily, those of us following NutritionFacts don’t have to wait for the next 5,000 studies!

  • livewire

    There always seem to be people who figure out aspects of these things well ahead of the pack. Dr Jane Plant in England, a science researcher, not an MD, had a breast cancer that was so persistent that, when it came back the fifth time, after all treatments and only days after yet another surgery, her doctors told her she probably only had two or three months to live. She began questioning what was the important difference between her diet and that of the Chinese, where she had done studies. At that time Chinese women had only one case of breast cancer in 100,000. She finally realized the Chinese didn’t eat any dairy products. She was only eating one yogurt daily, but when she stopped that her cancer quickly subsided. She developed a dairy-free anti-cancer diet and has helped thousands of breast and prostate cancer patients over the last 20 or 30 years to become cancer free.

    • Thea

      Very cool. Thanks for sharing.

  • Michael

    I wanted to re-ask the below question regarding TOR and muscle building in the context of leucine-rich plant foods since this blog post is related to the previous TOR video:
    ————————————–
    Dr. Greger,

    It seems that both signaling muscle protein synthesis (MPS) and aging prematurely (as discussed in this and previous video) involve the leucine/mTOR connection. Do you think, or is there research, that long life and building muscle mass are fundamentally opposed goals based on how our body is designed? Also, do you think, or is there research, that the mTOR theory of aging and leucine acting as a trigger could be meat/animal-protein specific? In other words, could eating leucine-rich plant foods in order to signal MPS still provide longevity benefits as well as muscle-building benefits? Kind of similar to the whole nitrate/nitrite conundrum where plant-sourced nitrates (from beets and arugula) get metabolized in the stomach and re-sent to the mouth where, instead of becoming carcinogenic nitrosamines (as is what happens when you consume nitrates from meat), they become NO and increase our oxygen efficiency. This seems plausible to me since you’ve praised pumpkins seeds (which are relatively high in leucine) in some past videos: (http://nutritionfacts.org/?s=pumpkin+seeds) specifically the mineral content and serotonin boosting effect.

    Research papers describing MPS and leucine signaling:
    http://www.ncbi.nlm.nih.gov/pubmed/16365096
    http://jap.physiology.org/content/106/6/2026
    http://www.biolayne.com/wp-content/uploads/Norton-J-Ag-Food-Ind-Hi-Tech-2008.pdf

    • A very interesting question this and something I’d like to hear more about. I’ve been weight training for about 24 years and have done all the supplements and protein shakes and eating lots of meat. I’ve been WFPB for 7yrs now and the last sports supplement I gave up 1yr ago was creatine, as it increases IGF-1 which is not desirable for adult health and longevity. So yes, the questions and points you raise are of great interest to me since I still want to increase strength and muscle mass even at the age of 38 after all these years of training… but want to do so on a WFPB lifestyle.

      • gtrdoc911

        Hey Scott, What WFPB foods do you find especially good for muscle gain. That is a concern for me as I find if I cut down my meat I start to thin out and I’m already too thin for my liking. Also it must be said most people on WFPB diet look rather emaciated.

        • Psych MD
          • Alan

            Thanks for the link Psych MD. I glanced at it and will read it as time allows !!!!

        • Sorry for the late reply. Psych MDs link below is very good. Kind of covers it really.

          I try to make a fresh veggie juice first thing in the morning (~400ml) after ~400ml of warm lemon water and a tsp of wheat/barley grass powder.

          Then either a green smoothie or a big bowl of rice/oat milk with oats + fresh cut up fruits/berries + a few nuts/seeds + avocado + a few dates + pea protein powder + tsp wheat/barley grass powder + tsp amla powder (taken from spoon) + tsp turmeric (again taken from spoon) + black pepper.

          Lunch might be sweet potato and beans or hummus and green leafy salad and tomatoes or rice and veg and nuts/seeds. We eat a lot of hummus in our household; my the children all under 6 love it. Same goes for broccoli and cauliflower.

          Dinner is similar.

          Snacks would include rice/oat cakes with almond/cashew butter or fruit or nuts or goji berries.

          I have very recently got into having some plain soy yoghurt (no added sugar) with seeds and nuts and goji berries or dried mulberries. Delish.

          I do enjoy the odd piece of vegan 70%+ dark chocolate. Just found a local craft chocolatier who makes amazing vegan chocolate. Another treat is the Almond Dream ice cream; best vegan ice cream I’ve ever tasted. Obviously these things are treats and occasional.

          So lots of energy dense foods most of the time and then some treats to save your sanity on our occasion.

          Oh and I have no health issues like high cholesterol, high blood pressure and don’t need to lose weight/fat etc etc so I can happily consume more nuts and seeds and avocados than maybe most can.

          Good luck

      • Fred

        I don’t lift weights but after exercising I take 5 of these…essential amino acids under the theory that these are “clean” aminos without the associated extras of meat or whey.

        http://www.swansonvitamins.com/swanson-ultra-ajipure-9-essential-aminos-formula-pharmaceutical-grade-60-veg-caps

    • pawel kapica

      Thanks for asking. I had the ery same question in mind that I asked as a response to prior articles and videos regarding TOR. One thing that comes to my mind is that muscle building doesn’t rely solely on mTOR and must be way more complicated that this one signaling pathway. When we look at vegan body builders and the increased number of high performance aththletes who are adopting a vegan diet around the world, it becomes clear that a vegan diet doesn’t inhibit muscle growth. many vegan athletes talk about an increased and improved regeneration. The question would be if their mTOR levels are decreased at all, or if the muscle stimulation through working out is enough to stimulate mTOR, or if again mTOR is not responsible solely for increased strenght and muscle building. I guess there must be another signaling pathway or process involved……kind regards

  • Elise

    Does whey share the same properties as milk or does the extraction make it better/worse in some way?

    • guest

      No way you should be eating whey! Get your nutrition from plants.

    • Rph1978

      “resistance exercise rapidly increases mTOR signaling and may decrease
      myostatin protein expression in muscle and that whey protein increases
      and prolongs the mTOR signaling response”
      Ref: http://www.ncbi.nlm.nih.gov/pubmed/19299575

    • Jim Felder

      My understanding from the videos posted here and other reading is that milk protein, including I would assume the proteins in whey, contains a ratio of amino acids that signals the body that it is time to grow! The proteins in whey could therefore be expected to signal the body to produce more of its own growth hormones like IGF-1 and reduce the production of IGF-1 binding protein. If the whey is dried, I would assume that the elimination of the water would make it much easier to consume larger quantities of the protein, and so if the resulting final food or beverage had a higher percentage of calories from protein than milk does would make the situation worse .

    • Whey is rich in leucine. http://www.wheyoflife.org/sites/default/files/Leucine-Content-in-Common-Foods.pdf
      Other amino acids–including glutamine, tryptophan and arginine–as well as palmitate (a fatty acid) and insulin (produced by the body in response to the sugars in milk) also promote TOR signalling. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581184/

      As Dr, Greger discusses elsewhere, the amino acid methionine, which concentrates in animal flesh and eggs, also drives cell growth. It leads to production of the hormone Insulin Growth Factor 1, which in turn promotes more TOR signalling. New research suggests that restricting methionine kills cancer stem cells and promotes longevity.

      As Daryll points out in one of his many wise comments on this blog, methionine is the sole amino acid that damages mitochondria, the part of the cell that functions as its power plant and controls how it burns fuel for energy. And many scientists are now suggesting that damage to mitochondria causes cancer and aging.

      For links to sources, more info on those scientists and a longer take on what’s wrong with protein, see http://eatandbeatcancer.com/2015/12/30/2016-whats-on-and-off-your-anti-cancer-platter/#more-3549

      • Thea

        Harriet: This is such a helpful answer! Lots of people have asked about whey before. I knew about casein, but wasn’t sure what to say about whey. This is important information. Thank you.

  • Lammie

    Hello, I am a regular reader, and since I take rapamycin for a rare lung disease (lymphangioleiomyomatosis), I read this story with particular interest. I am curious about the cancer stats. We are told that taking rapa (or sirolimus, as it’s also called) could *increase* some cancers in us, particularly melanoma. (I do not leave the house without SPF 30.) Can you speak any more on this?

    • robert

      After reading Dr. Greger’s post I was curious about if there was any research about rapamycin and melanoma. It turns out that there has been some. One example:

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525347/

      There is also an interesting article about how the intermittent use of rapamycin may be a better way to use it.

      http://www.sciencedaily.com/releases/2015/07/150706114120.htm

      • Jim Felder

        And in both of these articles they are using rapamycin to control the inflammation cycle of normal tissue, which as seen numerous times is very amenable to control with the right therapeutic diet, namely a WFPB diet, all without the potential side effects of the drug. So if isn’t already one of those 5000+ studies on rapamycin and mTOR, who is going to do the clinical trial with rapamycin in one arm of the study and a WFPB diet fully tailored to suppress mTOR in the other to see which works better in vivo?

        Maybe like other trials the effects could be measured initially in vitro by taking the blood of people eating a specifically tailored WFPB diet and those taking rapamycin and dripping it on different cancer lines to see which is better at suppressing mTOR expression and/or promoting cancer cell apoptosis. Could also mix some non-cancerous cells in with the cancer cells to see what the relative effect on the inflammatory response of the normal cells each treatment regime has when the combined cell culture is exposed to different chemotherapy drugs and protocols.

      • Fred

        Somebody should tie all this together?

        http://www.anti-agingfirewalls.com/2014/06/09/glucosamine-for-longevity/

        “The bottom line is that glucosamine supplementation lowers human mortality

        Glucosamine and Chondroitin Sulfate have already been shown in a large epidemiological study to lower overall mortality and reduce cancer risks – a 5-year study of 77,719 elderly residents of Washington State. We found several publications based on different analyses of data based on this population.

        Conclusions:

        For most of the supplements we examined, there was no association with total mortality. Use of glucosamine and use of chondroitin were each associated with decreased mortality.”

        Both of these papers were done on the same group of 77,719 people. We note that this is as great an effect as combining vegan diet and fish consumption! We find this quite surprising.

        * * Glucosamine appears to have a comparable or greater effect on mortality reduction and lifespan extension than Metformin, Rapamycin, 2DG, Veganism, and Resveratrol in nematodes and rodents. **

        RESULTS: Persons reporting use of glucosamine + chondroitin on 4+ days/week for 3+ years had a non-statistically significant 45 % lower Colorectal Cancer risk than non-users

        Epidemiological evidence exists that glucosamine and chondroitin supplementation reduces inflammatory biomarkers.

        Glucosamine supplementation may be protective against lung cancer.

        A 2010 publication suggests that taking *high doses* of glucosamine or prolonged use it glucosamine reduces levels of SIRT1, leads to apoptosis of pancreatic cells and could increase the risk of developing diabetes.

        http://www.anti-agingfirewalls.com/2014/06/09/glucosamine-for-longevity/

        This time the hazard ratio for mortality reduction is .82: 18% fewer deaths per unit of time for those consuming the supplement.

        Both of these papers were done on the same group of 77,719 people. We note that this is as great an effect as combining vegan diet and fish consumption! We find this quite surprising. Glucosamine appears to have a comparable or greater effect on mortality reduction and lifespan extension than Meformin, Rapamycin, 2DG, Veganism, and Resveratrol in nematodes and rodents.

  • vegank

    what would be interesting, is to see a research which shows what percentage of women with the breast cancer gene who stuck with WFPB , and those who didn’t , was diagnosed with cancer.
    I remember reading in Dr Greger’s book that Alzheimer’s for example is more like 30% genetics and 70% external/environmental factor, so could a similar hypothesis be applied to other health issues such as cancer?
    Studies such as the China study shows that those who did not have dairy in their diet seemed to have less chance of getting cancer, We could see the results had a significant correlation with their genetic make up or their standard western diet (unless there is already a research about this ). eg, if some didn’t end up with breast cancer in spite of continuing with the standard western diet, was it to do with genetics?
    Having said that I’m sticking with the WFPB diet .

  • san

    And then brocolli increases risks of chronic gastritisas studied in Japanese men, SURPRISE http://www.ncbi.nlm.nih.gov/pubmed/15471434

    • Lauren Hacker

      san, I read the study, thanks for the link. The study, while interesting, is more than 10 years old. Do you know whether subsequent research has been able to support or refute the findings?

      Also I saw no mention in the study about whether the broccoli eaten by the men was cooked or not. if it was cooked, the myrosinase enzyme needed to convert the broccoli’s sulforaphane precursor into sulforaphane (the anti-cancer, anti-h.pylori compound found in raw broccoli and other crucifers) would have been deactivated. In that case the levels of sulforaphane would have been so low that there would be no reason to expect eating more broccoli to decrease the risk of the mens’ chronic atrophic gastritis, but it was odd that eating more broccoli correlated with increased risk.

      The study raised more questions for me than it answered. Based on it I wouldn’t stop or cut back on eating broccoli and other crucifers daily.

      Dr. Greger talked about food prep techniques to maximize the levels of sulforaphane in crucifers here: http://nutritionfacts.org/video/second-strategy-to-cooking-broccoli.

  • Rick Z, MD

    Is it possible that dairy stimulation of tor could be a factor in sarcopenia of aging?

  • Mark

    My 7 year old daughter drinks raw whole organic milk from unstressed cows; how will that impair her health ?

    • Thea

      Mark: The problems with dairy are a long list, the vast majority of them having nothing to do with whether the milk is raw or organic or not. This page will get you started:
      http://nutritionfacts.org/topics/dairy/
      .
      You might also want to research diabetes since a high fat diet (yikes, *whole* milk!) is the root cause of type 2 diabetes. You can learn more about that and why avoiding milk is good from this page:
      http://nutritionfacts.org/topics/diabetes/
      .
      You might also want to research heart disease. They have found that 10 year old children in America (not true in more plant based cultures) are showing early signs of heart disease. This comes from the high cholesterol and saturated fat foods such as dairy, meat and eggs.
      http://nutritionfacts.org/video/heart-disease-starts-in-childhood/

      • Mark

        Thank you; and the cows are grass fed.

        • Thea

          re: grass fed. That’s better for the health of the cows, but it does nothing to affect the outcome of the links provided above. Good luck.

    • Jim Felder

      In addition to what Thea noted, much of the trouble with bovine breast milk is the high levels of protein and especially the amino acids methione and leucine. These two amino acids act as dietary signals to the body about whether or not it should be actively growing or not. When there is a lot of these two amino acids the body is stimulated to produce growth factors like IGF-1. Mammalian babies receive milk from their mothers that contain the amount of protein and especially the amount of these two aminos that is very carefully tailored to stimulate the growth rate appropriate for their species. The shorter the period of infant weight doubling the higher the percent protein is the milk in that species. Rats pups have one of the fastest doubling times and it is therefore no surprise that 49% of the calories in rat breast milks comes from protein. Human infants double in weight very slowly compared to other mammals and human breast milk contains one of the lowest protein percentages at around 6%. Calves double in weight at about twice the rate of human infants but about half as fast as rat pups and again not surprisingly bovine milk is about 22% of calories from protein.

      The endocrine response to this protein signalling doesn’t end at the age of weening, it is just that in the natural world the access to it is terminated by the mother. But we humans have done an end run around this natural termination of milk consumption and consume it into our adult years. Further the milk we appropriate comes from another species which produces milk with a much stronger growth signalling than we needed even as infants and definitely have no need of at all past weening. Continued consumption of bovine milk due to strong exogenous endocrine signalling can then be expected to have short and long term negative health consequences.

      In the case of young children such as your daughter the impact of milk consumption (and other animal foods since they too have higher levels of methione and leucine) could be precocious puberty. A primary concern here is that life-time breast cancer risk is a function in part of the age of puberty (as well as estrogen levels and age of menopause, which are also strongly influenced by animal food consumption including dairy). The sooner puberty starts, the more lifetime estrogen exposure and the higher the breast cancer rates. A century ago the average age of the start of menstruation in girls was 17. Now it is 12 1/2. Girls used to start developing breast at 12-13. Now they are starting to develop breasts as young as 5 and 6 years old. The talk about causes, such as in the linked paper above, is about endocrine disruptor chemicals like pesticides, fire retardants, BPA in plastics and the like, but from other videos on this site we know that a large percentage of our exposure to these endocrine disruptors come through bioaccumulation in the animals we collectively eat. Also there is mention of things like effect of circulating IGF-1 and IGF-1 binding protein on the age of puberty, but we know from many studies that the amount of IGF-1/binding protein is strongly influenced by the consumption of animal foods and especially milk. This study compare the age of puberty internationally. It looks at the age of puberty in girls in “well off” conditions as compared to those in the “impoverished” conditions. “Well off” is really just a euphemism for increase meat and dairy consumption and “impoverished” really means largely plant based since “impoverished” from a western perspective means not having all the meat, dairy and eggs to eat that a westerner would want. It doesn’t necessarily mean starving and malnourished. It shows that girls who live where they still eat a largely plant based diet still reach puberty at the same age that was common everywhere a century ago. Oh, and a lot of the papers that came up in my searchers were concerns about accelerated puberty in children adopted internationally by western parents compared to children in their country of origin. So it is clear that the genetics don’t play a role. Rural Chinese don’t hit puberty later just because they are Chinese. It is because they eat a largely plant based diet rather than a western diet.

      • Mark

        Thank you, for a different aspect of it’s negative side effects.

  • Judith Ronat

    Interesting article. But I didn’t find out what TOR stands for.

    • Ann Blanchard

      Target of rapamycin

  • Judith Ronat

    I see a site http://nutritionfacts.org/topics/tor/ but I couldn’t open the video or whatever. Please advise.