While I Was Sleeping

Somehow, while dozing off the effects of my Thanksgiving raclette, I missed the most important news yet regarding this blog’s favorite chemical.

Researchers believe they have identified a fundamental cause of aging, according to a study published this week in the journal Cell. The mechanism was previously found in fungus and has now been discovered in mice. It’s likely that the same process applies to humans, said the authors of the research, from Harvard.
The study found that DNA damage, which accrues as we age, decreases a cell’s ability to regulate which genes are turned on and off in particular settings. Though DNA damage speeds up aging, the actual cause is not the DNA damage but the lack of gene regulation. However, this lack of gene regulation, called epigenetics, may be reversible.

For a long time most experts assumed that a sort of unbreakable yin-yang relationship links aging and cancer. Researchers looking for a way to make cells live longer constantly ran into the problem that cancer happens when cells live too long. The perception was reinforced when attempts to prolong life by up-regulating a protein called telomerase, which protects cells from dying after they go through a given number of division cycles, repeatedly ran into cancer problems.

Via resveratrol, research into the sirtuin proteins shattered that misperception. They key, as described in the article, is that aging has less to do with cell death than it does with gene regulation. If we fix gene regulation, or reduce the rate that it slides into dysfunction, then at the cellular level we fight aging. It In fact the new research does better than that: cancer is also a disease of gene dysregulation. It turns out that the famous trade-off is one hundred eighty degrees wrong: if you upregulate DNA quality control then you fight aging and cancer at the same time. As it turns out, the list of other stuff that also starts to work better includes infectious diseases (i.e., we get less of them), mental productivity and cardiovascular fitness.

In fact researchers knew about the effect for decades. However, earlier studies accomplished longevity by cutting a rat’s dietary calories to a point that almost no human could bear. The break came when a team at Harvard guessed that the starvation benefit hinged on a DNA silencing protein called SirT1. When they tried a massive screen for SirT1-activating chemicals the #1 hit was resveratrol, a compound previously known only as a phenolic in red wine. Resveratrol made yeast live longer, it made worms live longer and it had the same effect on flies. Mice and rats followed. Then came a research boom that may never slow down.

It may seem silly that our bodies already have the machinery to live into a healthy old age but prioritize something else. Why do we essentially choose not to live as long as we could? The key insight is that resveratrol, like the starvation diet that it mimics, strongly inhibits the sex drive and reduces the lifetime reproductive output. Nature wants us to get busy, fast, which means that if we want our bodies to prioritize quality control over making whoopee we need to trick it into thinking that we are on the brink of death (dead animals don’t make babies, so the body activates survival mode). We can do that by actually almost starving to death, but it is nice to know that medical science could soon offer a plan B.

30 replies
  1. 1
    Just Some Fuckhead says:

    Please tell me this has no chance of keeping boomers around even longer.

  2. 2
    MNPundit says:

    So what would we die of? Disease, trauma? Otherwise live forever? Well as long as its restricted to Balloon-Juice readers…

  3. 3
    r€nato says:

    I’ve long believed that great advances to combat aging will be made in my lifetime…

    …but by the time they are available, I will be too old to benefit :-(

  4. 4
    r€nato says:

    those PJ Media ads at the left make me want to vomit. LGF? Charles Johnson? FOAD.

  5. 5
    Zifnab says:

    @MNPundit: I imagine there’s some functional upper limit. The human body is just too complex for shit to not ever break. But if it has the potential to prolong the inevitable by a decade or two more – and better still, to make those last years less shitty – hurray progress!

  6. 6
    Punchy says:

    I really wish people would stop the ridiculous and false correlation/causation mistake of turkey and drowsiness (and no Tim, I’m not suggesting you did). Ingestion of turkey does not cause an increase in drowiness. There exists evidence that a meal high in carbs jacks up the trytophan/neutral AA ratio, thus possibly causing more serotonin production, and thus the resultant effects.

    But turkey all by itself is not the cause, and it pains me that so many people believe in such nonsense

    /jumps off soapbox

  7. 7
    jenniebee says:

    Imagine Glen Reynolds’ disappointment when an effective Dorian Grey treatment makes his plans to be downloaded moot.

    Can I charge a shopping trip to Total Wine to my HSA now?

  8. 8
    Tim F. says:

    Ingestion of turkey does not cause an increase in drowiness.

    In my experience ingestion of a shitload of turkey, stuffing, gravy, mashed and sweet potatoes, three kinds of pie and ice cream absolutely does cause an increase in drowsiness.

    However, when I performed a control with a comparable amount of raclette cheese, potatoes, cured Italian meats, sausage, grilled vegetables and French apple tart [edit: and homemade creme brulee. yum] I got similarly drowsy. Hence the effects may not be specific to turkey. Will have to repeat next Thanksgiving.

  9. 9
    Joel says:

    IIRC, the pharmacokinetics of resveratol prevent it from having any significant dietary health benefits (i.e. its one thing to pour a chemical on cells in culture and its another thing entirely to actually ingest the chemical, have it pass through intestinal and liver metabolism, diluted in the blood stream, excreted, and make it through cell membranes and internal metabolic processes).

  10. 10
    That One - Cain says:

    I bet they never discuss this stuff on LGF.

    cain

  11. 11
    Tim F. says:

    IIRC, the pharmacokinetics of resveratol prevent it from having any significant dietary health benefits (i.e. its one thing to pour a chemical on cells in culture and its another thing entirely to actually ingest the chemical, have it pass through intestinal and liver metabolism, diluted in the blood stream, excreted, and make it through cell membranes and internal metabolic processes).

    Most of the studies that I know about have treated whole animals with dietary resveratrol. The problem is not so much that eating a pill won’t work, it is how much you have to eat. The pills on the market today should work but to get a mg/kg dose equivalent to the one that makes superrats you have to spend a ton of money.

    That said, the pharm companies are already working on an analog that should improve bioavailability, like acetylation did with salicylic acid (aspirin).

  12. 12
    Bill H says:

    But prolonging lifespan has a downside. Population increase has consequences. Can we not see that even as we speak?

  13. 13
    Punchy says:

    Hence the effects may not be specific to turkey

    And therein lies my point. Heavy ingestion of anything makes you sleepy. Mix in wine/alcohol and the effect is exacerbated. But turkey alone is not the cause.

    That said, the pharm companies are already working on an analog that should improve bioavailability, like acetylation did with salicylic acid (aspirin).

    I’m not so sure. A diphenyl alkene? That’s about as insoluable as they get. Funny: I was about to suggest buccal delivery, then I go to wikipedia and they say the same thing. Finally my grad skool edjumacation seems to be paying off.

  14. 14
    fester says:

    @TimF # 8 — ooahhh poor baby — that sounds absolutely delicious and it is the curse of science — having to suffer one’s own experiments on oneself :)

    PS: I love the edit countdown clock — nice little feature here.

  15. 15
    wibbles says:

    the population won’t increase. with a magicked-up reversatrol, you’d just have a dwindling population of long-lived narcissists lost in self-contemplation and low sex drive. it says right in the post that reproductive drives are reduced.

    i can’t imagine it has positive benefits for ovaries, eggs, endometrial lining, etc. in human women. it may even be that this drug mostly serves only to enhance male lifespans, with the complexity of the female body’s biochemistry offsetting the potential long-life effects.

  16. 16
    kwAwk says:

    Three weird thoughts come to mind…..

    First if this is true that we can reverse ageing and live to be 200 or forever how unlucky is that guy that gets run over by the bus at 23?

    And if you knew that the only way you could die is through accident or murder wouldn’t that make you especially paranoid and conservative in how you go about life?

    Lastly, if we know that this is a genetic thing that could be switched off and our bodies have the capacity to live much longer than they do, then doesn’t that invalidate one of the arguements against the Bible that says people lived to be 900 years old?

  17. 17
    stacie says:

    Wait, are you telling me that science has now found that deregulation causes aging, too?

    Geeze, when’s the GOP going to give it up?

  18. 18
    Zifnab says:

    @Bill H:

    But prolonging lifespan has a downside. Population increase has consequences. Can we not see that even as we speak?

    More advanced societies (ones that could afford to purchase the drug in large quantities) tend to have lower birth rates. And extending the lifespan with this kind of treatment also increasing the individual’s productivity. So you can have a guy at 60+ years old still working his job.

    It also gives older folks an incentive to invest in the future and consider long term global threats. I think part of the reason our society has a disdain for things like global warming, waste recycling, and renewable energies has to do with the elders in charge working under the assumption that these projected very bad things won’t happen in their lifetimes. So they can take a "What, me worry?" attitude. John McCain, for instance, doesn’t need to give a crap about food shortages in 2050, because he’ll be on the soylent green cart long before then.

    Longer, more robust lifespans are a good thing in the long run in my opinion.

  19. 19
    wibbles says:

    the perils of long lifespans are one thing the sci-fi nerds get right. there will be more self-absorption and less care of any environment other than the immediate ones each long-lived narcissist happens to occupy. it’s a bizarrely optimistic stance to presume that a mere doubling of lifespan would magically instill a love for mother gaia when it hasn’t worked to date with increased lifespans.

    worth noting that it’s the ‘advanced’ societies who create the pollution and destruction that they then flail arms about reversing. a few rich people living even longer is hardly the means to correct any impacts of human ‘advancement’. it is a complex question to wonder if it is truly advancement when the advances cause so much ecological and biological damage/decay.

    i mean, the societies having tons of children aren’t the pollution problem– it’s the ones having few or no children, and this shift is held to be an excellent thing by the no-children societies.

    i can easily see 200 year olds letting the world crumble while they squabbled to maintain their VR environments.

  20. 20
    Just Some Fuckhead says:

    What’s Dracula’s track record with a long life span? Not very good, I’m afraid.

  21. 21
    Svensker says:

    What’s Dracula’s track record with a long life span? Not very good, I’m afraid.

    But Dracula would have a different opinion of that.

  22. 22
    RedMolly says:

    So I can stop eating good food, quit having sex and extend my life for many many years so I can spend even more time not eating good food and not having sex? Wow, that sounds like oh so much fun.

    Off to drown my sorrows in some liquid resveratrol/ethanol solution.

  23. 23
    Comrade Sock Puppet of the Great Satan says:

    "The pills on the market today should work but to get a mg/kg dose equivalent to the one that makes superrats you have to spend a ton of money."

    Meh. It’s not that complex a molecule, so you’d think that manufacturing it wouldn’t be that much of a challenge. I just don’t think the scale or the process has been optimized yet. It’d certainly be less of a PIA than synthesizing Vitamin C or Vitamin A.

  24. 24
    The Crafty Trilobite says:

    it’s a bizarrely optimistic stance to presume that a mere doubling of lifespan would magically instill a love for mother gaia when it hasn’t worked to date with increased lifespans.

    You’ve got it exactly backwards, at least in the West.

    There’s a reason you don’t find landscape paintings in Western art before around 1800: nature scared the pants off of Europeans. Nature was "the wilderness" of the Bible, nothing more. Then we hit a good period — no Black Plague, a mild (temporary) climate improvement, exploitation of the other continents, global trade, and the beginning of the Industrial Revolution. Lifespan increased, and suddenly people had the leisure to look around and notice how pretty things were. Suddenly we see landscapes, we find Rousseau arguing that the "state of nature" was not "nasty, brutish, and short," but rather the source of all virtue, Keats writes about putting an urn on a bare hill. Next, we get Audobon painting birds and showing how amazing they look, rich Americans like Bronson Albott and Thoreau run away from the city to try to pretend to live natural lives, etc. After that, we get people like John Muir and even Teddy Roosevelt crying that we have to save the wilderness — now a term of praise, not horror. Finally, within our lifetimes, Earth Day, Gaia, and Wicca.

    It’s probably impossible to separate the effect of increased lifespan from the increased leisure made possible by greater wealth, but it’s far from "bizarrely optimistic" to expect some acceleration of the pro-Green trend if lifespan doubles.

  25. 25
    Robin G. says:

    Color me suspicious of any treatment that functions by tricking our bodies into thinking we’re about to die. Double that for a treatment that convinces our bodies not to reproduce.

    In the eyes of evolution, we have very limited purposes: Live to adulthood. Make babies. Keep babies alive until adulthood. Die. Our entire biology is built around those purposes. Medical efforts that fundamentally fuck around with that tend to have unintended consequences.

    Furthermore, pharmecutical-induced vampirism sounds hellish. What’s the point in staying young and healthy if it requires a double dose of Viagra and a quadruple dose of Wellbutrin to keep you from wishing for death?

  26. 26
    Tsulagi says:

    Okay, I’ve seen your posts on resveratrol before. Sounded like good stuff. While reading this post I was halfway thinking of googling to find its availability and cost as a possible supplement. Until I got to this part…

    The key insight is that resveratrol…strongly inhibits the sex drive… we want our bodies to prioritize quality control over making whoopee

    Some may have a different definition of “quality.” If my choice is to live into triple digits without whoopee, or check out at 70 during whoopee, I know which way I’m going. I ain’t touching that shit now.

    There’s always a catch.

  27. 27
    Brandon says:

    Sex drive…I don’t know if I’m speaking for others, but I could spare some of that in exchange for a longer life and not have any problems at all..

  28. 28
    Vincent says:

    There’s a catch now but it seems like the solution might be a matter of regulating some hormones. That’s usually what’s done with other types of treatments so that a patient still gets the benefits of the medication without having to suffer from impotence or whatever.

    In the eyes of evolution, we have very limited purposes: Live to adulthood. Make babies. Keep babies alive until adulthood. Die. Our entire biology is built around those purposes. Medical efforts that fundamentally fuck around with that tend to have unintended consequences.

    I’m sure the Pill has many unintended consequences but I would say that overall the benefits outweigh the risks.

  29. 29
    Robin G. says:

    There are indeed a lot of unintended consequences with the Pill. I too would say that the benefits outweigh the risks on a grand scale (at least the risks we’re clear on — research into the side effects of pharmaceuticals still have a long way to go). But there are not insignificant side effects of something that is, relatively speaking, a much smaller change (a hormonal tweak to convince your body it’s already done something it wants to do anyway). The side effects of, say, convincing your body it’s about to die in order to make you stop aging? I think it’s safe to say there may be some surprises along the way for the person who tries that.

    Also, to be clear, when I was saying that this treatment fundamentally fucks around with our basic goals, I was referring as much to the "Die" part as the "Make babies" part.

  30. 30
    Joel says:

    For what its worth, we’ve already extended our lifespan by simply providing the essential nutrients that our bodies have been deprived of for most of human history. Its worth revisiting the question of extending lifespan as if it were asked around, say.. 1940.

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