Why do we age?

Image Credit: Arian Zwegers / Flickr. This image has been modified.

Exploiting Autophagy to Live Longer

Thanks to advances in modern medicine, we are living longer lives, but we’re doing it by lengthening the morbidity phase. In other words, we live longer, but sicker, lives (see my video: Americans Are Live Longer, but Sicker Lives). So, traditional medicine increases the number of old people in bad health. Ideally, though, we’d extend lifespan by slowing aging to delay the onset of deterioration, rather than extending the period of deterioration.

That’s exactly what a new compound appears to do. It sounds like science fiction. A bacteria in a vial of dirt taken from a mysterious island creating a compound that prolongs life. And not in the traditional medical sense. Researchers in a study profiled in my video, Why Do We Age?, called it rapamycin—named after the bacteria’s home, Easter Island, which is known locally as Rapa Nui. Rapamycin inhibits an enzyme called TOR, or “target of rapamycin.” TOR may be a master determinant of lifespan and aging. The action of TOR has been described as the engine of a speeding car without brakes.

Rather than thinking of aging as slowly rusting, a better analogy may be a speeding car that enters the low-speed zone of adulthood and damages itself because it does not and cannot slow down. Why don’t living organisms have brakes? Because they’ve never needed them. In the wild, animals don’t live long enough to experience aging. Most die before they even reach adulthood. The same used to be true for humans. For example, just a few centuries ago, average life expectancy in London was less than 16 years old.

Therefore, living beings need to grow as fast as possible to start reproduction before they die from external causes. The best evolutionary strategy may be to run at full speed. However, once we pass the finish line, once we win the race to pass on our genes, we’re still careening forward at an unsustainable pace, all thanks to this enzyme TOR. In our childhood, TOR is an engine of growth, but in adulthood, it is the engine of aging. “Nature simply selects for the brightest flame, which in turn casts the darkest shadow.”

Sometimes, though, even in our youth, our bodies need to turn down the heat. When we were evolving, there were no grocery stores; periodic famine was the norm. So sometimes even young people had to slow down or they might never even make it to reproductive age. So we did evolve one braking mechanism: caloric restriction. Caloric restriction may extend lifespan mainly through the inhibition of TOR.

When food is abundant, TOR activity goes up, prompting the cells in our body to divide. When TOR detects that food is scarce, it shifts the body into conservation mode, slowing down cell division and kicking in a process called autophagy, from the Greek auto meaning “self,” and phagy meaning “to eat.” Autophagy essentially means eating yourself. Our body realizes there isn’t much food around and starts rummaging through our cells looking for anything we don’t need. Defective proteins, malfunctioning mitochondria, stuff that isn’t working anymore, and cleans house. Clears out all the junk and recycles it into fuel or new building materials, renewing our cells.

So caloric restriction has been heralded as a fountain of youth. The potential health and longevity benefits of such a diet regimen may be numerous, but symptoms may include dropping our blood pressure too low, loss of libido, menstrual irregularities, infertility, loss of bone, cold sensitivity, loss of strength, slower wound healing, and psychological conditions such as depression, emotional deadening, and irritability. And you walk around starving all the time! There’s got to be a better way, and there is. Check out my video Caloric Restriction vs. Animal Protein Restriction.

More tips for preserving youthful health:

-Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my videos for free by clicking here and watch my full 2012 – 2015 presentations Uprooting the Leading Causes of Death, More than an Apple a Day, From Table to Able, and Food as Medicine.


Michael Greger M.D., FACLM

Michael Greger, M.D. FACLM, is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous "meat defamation" trial.

34 responses to “Exploiting Autophagy to Live Longer

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  1. The simplest way to facilitate autophagy is to fast daily by limiting eating to a narrow window, about eight hours, during the day. Autophagy is known to increase the immunity, too, because the process can capture and kill bacteria inside cells and recycle the nutrients in them.

    1. I’m practicing this “intermittent fasting” approach at the moment, but would love to see what Dr. Gregor comes up with in terms of solid research out there… Great information. Love all the videos! Thank you!

  2. Yes, thanks Doc for this; mTOR signaling seems to spur cancer cell proliferation. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775843/

    Excess amino acids, glucose and insulin and oxidative stress activate mTOR signaling; many plants have phytonutrients that inhibit it. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039966/

    Leucine, an amino acid predominant in dairy, helps explain why milk sets off the wacky cell signaling system that leads to prostate cancer, says German dermatologist Dr. Bodo Melnik. Lots of links to his research here: http://eatandbeatcancer.com/2014/07/23/anti-cancer-diets-whats-the-deal-with-dairy/

  3. “…just a few centuries ago, average life expectancy in London was less than 16 years old.”

    I suspect that this average includes infant and childhood mortality. Whenever I look at the age when adults of a few centuries, or even quite a few centuries, ago died, the numbers are not that different from our times: 50s-70s or even later.

    1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672390/

      The crude average figures often used to depict the brevity of Victorian lives mislead because they include infant mortality, which was tragically high. If we strip out peri-natal mortality, however, and look at the life expectancy of those who survived the first five years, a very different picture emerges. Victorian contemporary sources reveal that life expectancy for adults in the mid-Victorian period was almost exactly what it is today. At 65, men could expect another ten years of life; and women another eight [24,32,33] (the lower figure for women reflects the high danger of death in childbirth, mainly from causes unrelated to malnutrition). This compares surprisingly favourably with today’s figures: life expectancy at birth (reflecting our improved standards of neo-natal care) averages 75.9 years (men) and 81.3 years (women); though recent work has suggested that for working class men and women this is lower, at around 72 for men and 76 for women [34].

      If we accept the working class figures, which are probably more directly comparable with the Victorian data, women have gained three years of life expectancy since the mid-Victorian period while men have actually fallen back by 3 years. The decline in male life expectancy implicates several causal factors; including the introduction of industrialised cigarette production in 1883, a sustained fall in the relative cost of alcohol and a severe decline in nutritional standards, as outlined below. The improvement in female life expectancy can be partly linked to family planning developments but also to other factors promoting women’s health such as improvements in dress. Until widespread accessible family planning facilities arrived after the First World War, women’s health could be substantially undermined by up to 30 years of successive pregnancies and births [35–37]. These figures suggest that if twentieth century women had not also experienced the negative impacts of tobacco consumption becoming respectable, along with an increased alcohol intake and worsening nutrition as they began to consume the imported delicacies originally preserved mainly for the men (all those things which had cost their menfolk three years), they would have gained six years.

      1. Thanks Charles. That article is a fascinating read.
        I seem to recall your name from a few years ago as a passionate advocate for the Dark Side of the Force! Or am I mistaken?

            1. Now I know what you mean – yes that was me – I’ve moderated my views on diet but I still consume animal products

  4. Dear Dr Gregor

    I love your site and have learnt so much but please I wish you wouldn’t use random facts that only tangentially relate to the point you make- “…just a few centuries ago, average life expectancy in London was less than 16 years old.” It detracts from your argument and makes you look a bit desperate. Evolution like this doesn’t work over a few centuries and of course the reason the figure is so low is because of death in childbirth which is the opposite of the point you are making.

    Nevertheless I forgive you. Keep up the great work..

  5. Dr. André Gernez works on cancer prevention propose a cancer prevention protocol validated on rodents with induced early-stage liver cancer:
    Group 1: Caloric reduction (~50% survival)
    Group 2: Caloric reduction + vitamin/minerals (~75% survival)
    Group 3: Caloric reduction + multivitamin + chemoprevention (~92% survival)
    => Result [1)] suggests autophagy is associated with cancer cell death when the cancer is in its early stage.

    Human equivalent is 30 days long and has been practiced in France since the 1970s.

    The books from the same author are in French, it’s really too bad. They are must reads for anyone interested in pioneering works. He integrated the stems cells into a theory of carcinogenesis (1968). Sadly “stem cells” and their relevance in cancer is mainstream medical knowledge today without his due acknowledgement.

  6. small request : replace term “traditional medicine” with orthodox or western medicine. TCM or First Nation herbalism would count as traditional in my book.

  7. How is this a new compound? The study you link to in the very sentence in which you call it “new” is from 1975… And even a cursory look into the research shows that it is associated with both a decrease but also an increase in different forms of cancer risk.

    It is, anyway, unclear what the point of this piece is—it’s hardly possible or medically advisable for your readers to start speculatively taking rapamycin in an attempt to lengthen their lifespans. What was the intention here?

  8. I also practice daily “IF.” It’s 1:45 and I just finished lunch consisting of carrots, celery and apple slices dipped in hummus topped off with a sweet potato. Throughout the morning I consumed two cups of coffee and four cups of a variety of teas: a green/white blend, a green/hibiscus/lemongrass blend, and Celestial Seasonings Indian spice which is black tea with cinnamon, cloves, and other great stuff. I have an office in the hospital where I can come and go seeing patients at my own pace. I challenge myself to see as many as possible before I have any food. I have conditioned myself to not even THINK about eating till at least noon. It is really amazingly simple. As far as the comment below re: a 12 hour feeding window, I doubt that would qualify for IF or achieve the effects of calorie restriction. That is essentially eating from 10 AM to 10 PM. Not much “hormesis” occurring there.

  9. In the subject autophagy and cancer, there’s an
    interesting work done by Dr. Michael Lisanti, an american researcher in
    cancer treatment now working in Manchester, UK. Without going into
    details that can be seen HERE, he says both autophagy inducers and autophagy inhibitors can kill cancer cells: he calls this the autophagy paradox. To solve this paradox, he suggests
    the best strategy is to give alternating autophagy inducers and
    autophagy inhibitors to cancer patients – this will “confuse” the
    cancer, and the tumor will die. So, translating this to a day to day living, it’s probably a good idea alternate caloric restriction with non-caloric restriction…?

    1. Since Dr. Lisanti’s theory seems to work in reducing tumor masses, I believe there are foods that work as autophagy inducers and foods that work as autophagy inhibitors, too – so this should be interesting to be “put into the test”… ;)

  10. Disagree. At 80 I’m doing far better than any of my ancestors. Feel fine, exercise, vegetables, fruits, whole grains, beans, peas, nuts, B12 ….Fitness exercise most days. My wife slightly younger just did a 5K first in her age group. At Fitness there are people in their 80’s and 90’s doing just fine. No pharmaceuticals.

    Now I have a couple health situations which cause me no problem. I’ve had squamous cell carcinoma’s removed heal fine. Doubtless sunburns decades ago. I have atrial flutter dating from a bad cold in 2004, where my atrium beats at 270 but my ventricle beats at 70. This is not Afib. I get a cardiologist checkup yearly. No treatment advised, no aspirin even. Feel fine, bicycle up steep hills (this is NH) not out of breath no heart stress.

    There are people around here who look much older than I am but were born later. That’s their choice. The doctors that prescribe whatever the fashionable and expensive pharmaceuticals need to heed: http://nutritionstudies.org/major-medical-center-offers-plant-based-programs/. A couple relatives in the medical industry may be headed in that direction very slowly since nutrition isn’t taught in medical school and research in the U.S. is funded by pharmaceuticals thanks to Republicans cuts to NIH. NIH did fund a rat longevity study for T.Colin Campbelll in “The China Study” (funded by Premier Chou Enlai who had cancer). Essentially rats on 20% protein died or were very sick at usual life span while rats on 5% protein were in great shape.

    1. Jerry I was just talking to someone about this very thing. At 5 and 10 k races one sees the fittest individuals during the award ceremony–in all age groups. Truly inspiring. 80 years olds are getting around as well as the younger racers.

  11. In the book How Not to Die the growth hormone shortens life span. Ironically fasting boost growth hormone but also this youth serium of autophagy.

    I’m waiting for Michael Gregers new book. This week there was a video interview posted on YouTube saying he is on the fence about this subject of intermittent fasting and there will be a chapter in his new book.

  12. The TOR pathway is activated during the protein uptake phase and the protein synthesis phase, two very different processes…

    Animal proteins uptake may promote disease, but physical exercise promotes health: two different mechanisms in which TOR is involved in.

    If protein synthesis is required while protein supply is low, TOR may promote autophagy and get rid of damaged cells.

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