Monkeying Around with the Data on Calorie Restriction?

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Last week, two research teams reported to great fanfare that restricting the calories consumed by rhesus monkeys had extended their lifespans. Calorie restriction is thought to increase longevity by boosting DNA repair. The idea is that the mechanism evolved so that creatures on the verge of starvarion could live long enough to reproduce when food becomes plentiful again. But did the experiments really show the CR works?

In my earlier blogpost on the research results, I noted that some experts quoted in the New York Times were not convinced. Why? Because the difference in actual death rates between the dieting monkeys and the free feeding monkeys was not statistically significant.

Food policy blogger, Sandy Szwarc, looks at the reported results at Junkfood Science and finds them severely wanting. Among other things, Szwarc argues:

The lower mortality claimed among the monkeys on the calorie restricted diet were achieved only after eliminating 37% of the monkey deaths. They defined mortality as "age-associated deaths" and eliminated any cause of death they didn't believe was associated with aging. As the supplemental data explains, 16 deaths from "non-age-associated causes were censored and their age of death used as the time variable in the regression."

Science doesn't really work that way. Researchers can't simply ignore the evidence that doesn't support their hypothesis. That would be the difference between research done to build evidence to support a hypothesis, from science that is objectively studying a hypothesis…

The non-aging-related causes of death included monkeys who died while taking blood samples under anesthesia, from injuries or from infections, such as gastritis and endometriosis. These causes may not be aging-related as defined by the researchers, but they could realistically be adverse effects of prolonged calorie restrictions on the animals' health, their immune system, ability to handle stress, physical agility, cognition or behavior.

As we know, the most important endpoint in medical interventions is all-cause mortality. Selectively looking at only one cause of death, while ignoring that more patients died from something else, is not evidence to support the efficacy of a treatment. "The treatment worked, but the patient died" is not good medicine that considers the whole patient.

Assume that the dead dieting monkeys were properly excluded on the grounds that they died of non-age-related causes, there is other evidence that suggests that being too skinny is not healthy. A 2003 study by British researchers found that underweight people (body mass index below 18) are more likely to die (at a younger age*) than are average or slightly overweight people. That finding was bolstered by a new Canadian study reported last month. Not surprisingly, people who practice calorie restriction tend to have below average BMIs.

So while there is suggestive evidence that calorie restriction may increase longevity, the case is not yet proved.

Hat tip to Andrew Mayne.

*clarified

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  1. Even if it is true, who cares. I don’t see how living a few extra years in your 80s and 90s is worth spending your entire life living like a monk starving yourself.

  2. Any time I read one of these “Privation X might make you live slightly longer” stories, I am always reminded of that Onion classic.

    World Death rate Holding Steady at 100 Percent.

  3. Even if it is true, who cares. I don’t see how living a few extra years in your 80s and 90s is worth spending your entire life living like a monk starving yourself.

    But, John, if they can just make it 20 more years they will live to the Singularity and never die.

    I swear to god I read that in an article (online, of course) in the NYTimes.

    And when you say “like a Monk” you really mean it because these diets also reduce libido. I basically have the same belief as you when it comes to eating “right”, smoking, and drinking. So I can be decrepit at 90? Thanks anyway.

  4. You know, at a certain point science seems to inevitably turn into just some dude being a dick to a bunch of monkeys.

  5. John & Marshall Gill: Who wants to live to be 100? Someone is 99 years old.

  6. Eating too much OR too little is unhealthy, right?

    The kind of food you eat is at least as important as how much you eat, a well. Wouldn’t 3000 calories worth of healthy foods be better than 1000 calories worth of junk food?

    I guess I can’t say for sure, because I don’t have a bunch of monkeys and a furnace into which to burn grant money.

  7. *as well

    Preview is my friend.

  8. So, what they’ve proved is that calorie restriction makes you live longer, if calorie restriction doesn’t kill you first? Good to know…

    They also need to measure the effect of the calorie-restricted monkeys living longer in the hope they could escape and beat the shit out of the bastards who had been starving them all this time. Revenge is not only a dish best served cold, it’s very filling.

  9. Who wants to live to be 100? Someone is 99 years old.

    The implied universal in this sentence is unwarranted.

  10. Who wants to live to be 100? Someone is 99 years old.

    Surviving to be 100, even if you are already 99 is not the same as “living”.

    If I had lived 99 years, hell 43, for that matter, I would want to enjoy what I had left. Sure, some people would be placed in cryogenic sleep, so that they could “live” longer. Human narcissism knows no limits.

  11. “John & Marshall Gill: Who wants to live to be 100? Someone is 99 years old.”

    Ron,

    Not really. If your quality of life is low and all of your friends and spouse and children have died, you might not want to live much longer. Not that I plan to kill myself at 99, but unless there are massive improvements in the quality of life for those over about 85, I am at best ambivilent about how long I live after about that age. I know several people that age who feel the same way. They are not killing themselves, but if they were to get a terminal disease, they wouldn’t subject themselves to long painful treatments.

    At some point you have to reconcile yourself with your mortality.

  12. They also need to measure the effect of the calorie-restricted monkeys living longer in the hope they could escape and beat the shit out of the bastards who had been starving them all this time.

    Very nicely played, Sir!

  13. Eating too much OR too little is unhealthy, right?

    Lemme check…

    Yup. Karen Carpenter and Mamma Cass Elliot – still dead today.

  14. Waitaminnit, where’s my grant money?

  15. Yeah, Karen Carpenter was 32 at her death on February 4, 1983. Michael Jackson was 50.

    Upshot: Eat, drink and be merry!

  16. Bailey,

    Are you saying that if I’m participating in a drug trial and get hit by a bus, my death should count as a death caused by the drug? ‘Cause that doesn’t sound like good science either.

    But, John, if they can just make it 20 more years they will live to the Singularity and never die.

    I swear to god I read that in an article (online, of course) in the NYTimes.

    What’s wrong with that? The confident prediction of a time scale is silly, but if science continues to advance there eventually will be someone who could have lived forever if they had held on for a few more years [or a few more days, or hours]. Who wants to be that guy?

  17. Fluffy,

    What if the drug caused you to forget to look both ways?

  18. Scientists can be callous bastards. Ever see the stress and sleep deprivation experiments where animals are placed on tiny platforms surrounded by water? That is awesome cruelty.

    I like the experiments where rats and monkeys are given unlimited access to recreational drugs. It’s edutainment I tell yah!

  19. Damn dirty apes or just poor mal-nourished monkeys?

  20. What’s wrong with that? The confident prediction of a time scale is silly, but if science continues to advance there eventually will be someone who could have lived forever if they had held on for a few more years [or a few more days, or hours]. Who wants to be that guy?

    I wasn’t suggesting that people shouldn’t be free to dream, dude. But who wants to be an idiot and forgo food and sex so that, maybe, hopefully, they can be that guy? Not me.

    Wouldn’t it be ironic for some of these people to be struck by lightning? Killed in car accidents? Like this “study” shows, there are more causes of death than eating too many calories.

    It is a religion. You forgo the current certain life for promises of eternal life, later. Just like other religions, I personally, will pass.

  21. “It is a religion. You forgo the current certain life for promises of eternal life, later. Just like other religions, I personally, will pass.”

    I will take my chances with God as opposed to some scientist starving monkeys for grant money.

  22. They’re clearly leaving something out here.

    In any good experiment, you have a “test” group and a “control” group.

    Obviously the test group lived longer than the control group, or the study never would have gotten notice.

    But people here are suggesting that there’s statistical malfeasance at work, by which the test group only lives longer if you exclude non-age-related deaths.

    To understand the case, you MUST look at the non-age-related deaths amongst the control group.

    I.e. if 12% of the test group died by non-age-related causes, and 12% of the control group died by non-age-related causes, then the study has no problems whatsoever by excluding those.

    But if 29% of the test group, and only 12% of the control group died from non-age-related causes, the charges of statistical malfeasance would stick.

    From supplemental data linked by the Junkfood Science blogger, it shows that 16 animals died of causes they considered “non-age-associated”. Of these 16, 7 were in the control group, 9 were in the calorie-restricted group. There were 26 animals in the calorie-restricted group, 16 in the control group. Thus, about 35% of the calorie-restricted animals died of non-age causes, and about 44% of animals in the normal dietary group died of non-age causes.

    This is much ado about nothing, folks.

  23. They had to anesthetise monkeys for blood samples? Wimps.

  24. Monkeying Around with the Data on Calorie Restriction?

    RACIST!!!!!

  25. All I can say is that “Consumed by Rhesus Monkeys” would make a fantastic band name.

  26. The nice thing about this study is that it means after Team Obama is through with our economy, and 60% of our farmland is devoted to growing biofuels, we’re going to have some serious longevity increases.

    By “we” I mean those of us who aren’t union bosses or high-powered Dem campaign contributors.

  27. “What about monkey, Dee? They’re like nature’s humans.”

  28. This sentence really irked me:

    A 2003 study by British researchers found that underweight people (body mass index below 18) are more likely to die than are average or slightly overweight people.

    The last time I checked, your likelihood of death is 100%, regardless of weight.

  29. you cannot kill that which never lived!

    BWHAHAHAHAHAHHAHAHAHAHHAHAHAHA!!!

  30. It is a religion. You forgo the current certain life for promises of eternal life, later. Just like other religions, I personally, will pass.

    No, not really.

    When my son was born we opened a tax-free education savings account.

    Doing so was a bet. I’m trying to anticipate the future state of higher education, the economy, my life situation, etc., and making an investment now based on that bet.

    If it’s not stupid to make financial bets based on outright guesses of what the world will look like in 20 years, why is it stupid to make lifestyle bets based on a guess about the state of science in 40 years? Obviously the latter is measurably more difficult to do than the former, even based only on the time horizon involved – but is it so much harder to do that it’s a religion?

  31. Brad nails it. There were just as many non-age-related deaths (more actually, proportionally) in the control group than in the experimental group. I’m still skeptical about the science of CR (and probably not convincible that it is worth doing myself in any case) but the researchers are above-board here on the exclusion of animals from the study.

    Experimental animals die. They also get sick, get in fights with their littermates, have weird reactions to anesthesia, etc., etc. Demanding that no animals be excluded from a study for any reason is an impossible standard.

  32. Who wants to live to be 100? Someone [who] is 99 years old.

    Actually the only person that old that I know is 101. And she has clearly stated that she would be quite happy to quietly slip away. And this is a woman who is stil lucid and mobile. She’s in better shape than people twenty years younger.

  33. Not that that proves anything, of course.

  34. If it’s not stupid to make financial bets based on outright guesses of what the world will look like in 20 years,why is it stupid to make lifestyle bets based on a guess about the state of science in 40 years?

    Outright guesses? How many millions of people have invested and profited? In the very next sentence, you answer your own question.

    Obviously the latter is measurably more difficult to do than the former, even based only on the time horizon involved

    There is a historical basis for your belief that a financial investment will produce future benefits. There may never be a Singularity, or eternal life. While your investments may fail, or be stolen or defrauded from you, you can actually see millions of times that it did work. Not one person who has starved themselves has lived forever, not one.

    Should I assume from your comments that you are only consuming 1500 calories a day? Why not? Oh, because it is stupid.

  35. The big point I see made from many people is about the exlcusion of non age
    related deaths. But I believe most of these occured earlier in the study
    when the monkeys still weren’t in old age. The monkeys are given anesthesia
    once or twice a year! (what the hell has this got to do with aging?) so
    damn right it should be excluded. Gastric bloat I believe is caused by over
    feeding at any one time or something, and can happen at any age (again it
    does not tell you shit about aging rate because its non age related). Head
    trauma or other injuries that result in death are once again showing us
    absolutely nothing about the rate of aging. All these issues were better
    taken care of later into the study.

    Being reasonable here, it’s very sensible and fair to exlcude non age
    related deaths

  36. Let’s ask the Breatharians, shall we?

  37. Yeah! Like I am so down with the Breatharians. Thanks Nooge!

    “there are always people who want to ‘up the annie’ by increasing the intensity of the sensations”

    I always dream of upping the annie in the 5th dimension.

  38. Durrr: Point taken and clarified. Thanks.

  39. Matthew, the fact that the CL animals died more readily when stressed (during blood draws) and died more readily from gastritis (infections and lowered immunity) are both recognized effects of undernutrition and starvation — in other words the effects of calorie reduction. Whether the deaths were aging related is a nonissue. CL is what is being tested and it failed to reduce all-cause mortality, it just changed the cause of death.

  40. After looking into this a bit more I have been able to write up why excluding non age related deaths is important, and the rational behind this. You cam check my blog post out if you’re interested.

    The monkeys never died from infections, neither did they die from gastritis. Gastric bloat was caused by a batch of overcooked food at one point in the study. A totally preventable death. Other deaths were from anesthesia but were not related to increasing age, and also accidents like head trauma, which again tells you essentially nothing about whether cr was working or not. Please do check out my post on my blog. I’ve linked my name to the cr blog

  41. Look up “competing risks”.

  42. There were 38 control monkeys and 38 hungry monkeys. Brad and B, check your math. The researchers said that without excluding the deaths from low vigor* the death rate was statistically similar.
    *endometriosis, gastric bloat, and anesthesia.

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