EAT LESS AND LIVE LONGER

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    Aug 14, 2008 6:28 AM GMT
    Eat Less, Live Longer? Gene Links Calorie Restriction To Longevity

    ScienceDaily (May 2, 2007) — In studies going back to the 1930's, mice and many other species subsisting on a severely calorie-restricted diet have consistently outlived their well-fed peers by as much as 40 percent. But just how a diet verging on the brink of starvation extends lifespan has remained elusive.

    Now, researchers at the Salk Institute for Biological Studies have cracked open the black box of how persistent hunger promotes long life and identified a critical gene that specifically links calorie restriction (CR) to longevity.

    "After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular program required for increased longevity in response to calorie restriction," says Andrew Dillin, Ph.D., an associate professor in the Molecular and Cell Biology Laboratory, who led the study published online in the May 2 issue of Nature.

    Having identified a key link between calorie restriction and aging also opens the door to development of drugs that mimic the effects of calorie restriction and might allow people to reap health benefits without adhering to an austere regimen that only ascetics can endure.

    Initially, researchers thought that the effect of calorie restriction on aging was mediated through insulin-like signaling pathways in the roundworm Caenorhabditis elegans (C. elegans), but experiments by graduate student Siler Panowski in Dillin's lab suggested otherwise.

    In the worm, signals passed down the insulin/IGF-1 pathway regulate a DNA-binding protein called DAF-16 that belongs to what is called the forkhead family. It was believed that DAF-16 then regulated expression of genes associated with longevity. Dillin had also identified a co-regulator in the pathway called SMK-1 that apparently worked with DAF-16 to regulate longevity.

    "When we asked whether DAF-16 and SMK-1 proteins were both necessary for CR-mediated longevity, DAF-16 turned out to be unnecessary but, somewhat surprisingly, SMK-1 was," says first author Panowski.

    Since 15 other forkhead-like factors are expressed in C. elegans, graduate student Suzanne Wolff and former post-doctoral fellow Hugo Aguilaniu, Ph.D., now an assistant professor at the École Normale Supérieure de Lyon, France, set out to determine if any of them teamed up with SMK-1 to delay aging in the CR-response. They did this by knocking out each gene separately and observing whether the genetically altered worms still showed enhanced longevity when calorie-restricted.

    Loss of only one of the genes, a gene encoding the protein PHA-4, negated the lifespan-enhancing effect of calorie-restriction in worms. And, when researchers undertook the opposite experiment--by overexpressing pha-4 in worms--the longevity effect was enhanced. "PHA-4 acts completely independent of insulin/IGF-1 signaling and turns out to be essential for CR-mediated longevity," says Panowski.

    So far, only one other gene, called sir-2, has been implicated in the life- and health-prolonging response to calorie restriction. Increased amounts of SIR-2 protein extend longevity of yeast, worms, and flies, but while loss of sir-2 disrupts the calorie restriction response only in yeast, it has no effect on other organisms, such as worms.

    "We know three distinct pathways that affect longevity: insulin/IGF signaling, calorie restriction, and the mitochondrial electron transport chain pathway, yet it is still not clear where sir-2 fits in. It seems to meddle with more than one pathway," says Dillin and adds that "PHA-4 is specific for calorie restriction as it does not affect the other pathways."

    Humans possess three genes highly similar to worm pha-4, all belonging to what is called the Foxa family. All three play an important role in development and then later on in the regulation of glucagon, a pancreatic hormone that unlike insulin increases the concentration of blood sugar and maintains the body's energy balance, especially during fasting.

    The potential payoff for cutting to 60 percent of normal while maintaining a healthy diet rich in vitamins, minerals, and other nutrients, is huge. Currently it is the only strategy apart from direct genetic manipulation that consistently prolongs life and reduces the risk of cancer, diabetes, and cardiovascular disease, while staving off age-related neurodegeneration in laboratory animals from mice to monkeys. Although some people are already imposing this strict regimen upon themselves, it is too early tell whether calorie restriction will have the same effect in humans.

    Graduate student Jenni Durieux also contributed to the study.

    The work was funded by grants from the NIH, American Diabetes Association and the Ellison Medical Research Foundation.

    source: http://www.sciencedaily.com/releases/2007/...70502143834.htm
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    Aug 14, 2008 6:36 AM GMT
    Funny enough, we Asians and Indians (South Asians) with our propensity for famine and asceticism are often the people with the longest lifespans (barring unnatural death causes):

    From Wikipedia:

    Some populations have a reputation of producing unusual number of individuals with exceptionally high ages, for example:

    * Okinawans,
    * people from the mountains of Pakistan the Hunza,
    * the inhabitants from the high mountain valley of Vilcabamba in South America,
    * inhabitants of some regions in the Caucasus mountains.


    I say isolate it, whatever it is and give it to us in pills. LOL

    I wouldn't want to live longer if it meant I get to be a wasted husk of a man. icon_wink.gif

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    Aug 14, 2008 12:34 PM GMT
    There is no way in hell, I ever want to be 70, or even 80. I have already lived along full life.

    eat drink and be merry, for tomorrow you may be hit by a bus.

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    Aug 14, 2008 12:39 PM GMT
    Pattison saidThere is no way in hell, I ever want to be 70, or even 80. I have already lived along full life.

    eat drink and be merry, for tomorrow you may be hit by a bus.



    I sort of agree with you Pattison. It is the quality of the life not the quantity that is important. And I was almost hit be a car this morning walking to work. Some idiot who did not bother slowing down making a right turn on a red light. icon_evil.gif
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    Aug 14, 2008 2:10 PM GMT
    Id rather die at 70 than live until Im a 100yo anorexic twink.icon_rolleyes.gif
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    Aug 14, 2008 2:24 PM GMT
    SurrealLife said
    Pattison saidThere is no way in hell, I ever want to be 70, or even 80. I have already lived along full life.

    eat drink and be merry, for tomorrow you may be hit by a bus.



    I sort of agree with you Pattison. It is the quality of the life not the quantity that is important. And I was almost hit be a car this morning walking to work. Some idiot who did not bother slowing down making a right turn on a red light. icon_evil.gif


    I have to agree here. I see no point in life, if you are a vegetable, or cannot even get out of bed without help. I hope that I will live to about 70, and then die peacefully in my sleep (I wish!).
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    Aug 14, 2008 7:52 PM GMT
    Wow, I'm surprised by all the morose posts from people saying they don't want to live past 70. I look at people like Jack LaLane and Mike Wallace who are active and fit into their 90s and I think "I want to be like that."

    If I die before I'm 80, I'll feel I was cheated of some good years left to go.
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    Aug 14, 2008 10:34 PM GMT
    I don't ever want to die!

    So should I stop eating now?
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    Aug 14, 2008 10:44 PM GMT

    EAT MORE AND LIVE FULLER!
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    Aug 15, 2008 1:16 AM GMT
    Global_Citizen saidWow, I'm surprised by all the morose posts from people saying they don't want to live past 70. I look at people like Jack LaLane and Mike Wallace who are active and fit into their 90s and I think "I want to be like that."

    If I die before I'm 80, I'll feel I was cheated of some good years left to go.


    Not morose at all, but I believe a long life does not necessarily equate to a happy life. Sometimes I think our society is becoming too neurotic about health issues and not concerned about the quality of life. We are becoming a society of hypochondriacs.
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    Aug 15, 2008 1:32 AM GMT
    Global_Citizen saidWow, I'm surprised by all the morose posts from people saying they don't want to live past 70. I look at people like Jack LaLane and Mike Wallace who are active and fit into their 90s and I think "I want to be like that."

    If I die before I'm 80, I'll feel I was cheated of some good years left to go.


    Tell you what. Go work as a nurse in aged care, and care for all the people whom may live until 80, or 90, 105. Whom to just have piss is an effort, let alone everything else. Whom are unable too feed themselves.

    People whom spend 20 years in bed, as a vegetable.

    People whom beg for the right to die, because they have had enough. Maybe you don't get to see these people, hidden away. This side of getting old.

    They will tell you it's not quantity, but quality, and Once your health is gone, so should you.

    So if you want to call us whom don't want to be 70 or 80 morons, I hope you live until 105. What a curse, this would be.
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    Aug 15, 2008 1:40 AM GMT
    Michael Phelps is eating 12,000 calories a day. Is he taking years off of his life?

    icon_lol.gif

    All kidding aside, there's a similar study going on at Hopkins right now. Interesting stuff.

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    Aug 15, 2008 2:24 AM GMT
    Personally, two of my grandparents died before I was born. One other, suffered multiple strokes, and became less and less mobile, eventually living like a vegetable before dying (a period of a few years). My last remaining grandparent (she's 98 now) is currently in a nursing home. She is now bed-ridden, hardly ever opens her eyes, and is on a liquids-only diet. I really don't see much point in living, if I were in either position. Compare that with my father, who died in his sleep at age 72. Now, that's the way I want to go.
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    Aug 15, 2008 5:08 AM GMT
    My Gramma lived to almost 101. She was 99 and still living in her home and going upstairs to go to bed. She was too darn stubborn to move a bed downstairs. She finally went to a "retirement community" because she fell and got spooked. About a month after she was there she suffered a stroke and was never the same. But to be almost 100 and still as vibrant and sharp as ever, I hope I got those genes.
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    Aug 15, 2008 2:45 PM GMT
    Pattison said
    Tell you what. Go work as a nurse in aged care, and care for all the people whom may live until 80, or 90, 105. Whom to just have piss is an effort, let alone everything else. Whom are unable too feed themselves.

    People whom spend 20 years in bed, as a vegetable.

    People whom beg for the right to die, because they have had enough. Maybe you don't get to see these people, hidden away. This side of getting old.

    They will tell you it's not quantity, but quality, and Once your health is gone, so should you.


    Well, you quoted me, but it seems you may have missed the part where I said "active and fit into their 90s."

    So if you want to call us whom don't want to be 70 or 80 morons, I hope you live until 105. What a curse, this would be.


    Take a second look. I said "morose", not "morons".

    mo·rose
    –adjective
    1. gloomily or sullenly ill-humored, as a person or mood.
    2. characterized by or expressing gloom.

    One should learn to read a little more carefully.
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    Aug 15, 2008 3:02 PM GMT
    Global_Citizen said
    Pattison said
    Tell you what. Go work as a nurse in aged care, and care for all the people whom may live until 80, or 90, 105. Whom to just have piss is an effort, let alone everything else. Whom are unable too feed themselves.

    People whom spend 20 years in bed, as a vegetable.

    People whom beg for the right to die, because they have had enough. Maybe you don't get to see these people, hidden away. This side of getting old.

    They will tell you it's not quantity, but quality, and Once your health is gone, so should you.


    Well, you quoted me, but it seems you may have missed the part where I said "active and fit into their 90s."

    So if you want to call us whom don't want to be 70 or 80 morons, I hope you live until 105. What a curse, this would be.


    Take a second look. I said "morose", not "morons".

    mo·rose
    –adjective
    1. gloomily or sullenly ill-humored, as a person or mood.
    2. characterized by or expressing gloom.

    One should learn to read a little more carefully.


    One noticed your first point. But only few live to old age with good health. But with 50 knocking at my door, it is so close, One can hear it squeak. Yet If I was too die in my sleep tonight. I would not feel I've missed out on anything. I've lived a full life. The only reason I took up smoking, it is my passport out of here and not into old age. yet this may fail.

    I stand corrected on your second point. yes sometimes One should read more carefully, and put on One glasses; One of my first curses of old age.

    But still eat drink and be merry, as you may well be hit by a bus tomorrow. How many people walk out of their front door, to never go back in it again. it's a fact of life, and so is dying.
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    Aug 15, 2008 3:13 PM GMT
    Pattison said
    But still eat drink and be merry, as you may well be hit by a bus tomorrow.

    I try to live life to the fullest everyday. And there's no reason I shouldn't want to do that into my 80s, 90s, or even 100s if I should be so lucky.
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    Aug 15, 2008 3:18 PM GMT
    Who want to live past 80? Just start asking guys who are 79. I doubt that most if any at all would be saying "I don't want to live into my 80's!"

    The study is interesting, but it's somewhat myopic. It's far easier to study something and ignore the sometimes countless other variables that are both environmental as well as congenital. The more of this sort of thing you leave out, the easier it is to make a point.

    Anecdotally, my own grandmother who was never thin (though never obese during my lifetime) lived a full life and was self-sufficiently active until she died at 99, one week short of her 100th birthday. I'd be perfectly happy to live as well.
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    Aug 15, 2008 3:21 PM GMT
    Chuy2010 saidId rather die at 70 than live until Im a 100yo anorexic twink.icon_rolleyes.gif


    Holy crap that's funny! icon_lol.gif
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    Aug 15, 2008 3:26 PM GMT
    Let me also say I realize that things diminish as you get older, but that doesn't necessarily mean I would want to hang it up. You adapt.

    I know I can't run a 5K as fast as I could when I was 22. I don't have as much hair as I did at 22. I now have to wear contacts. As I age, there will be other things that diminish. And I'll adapt to that too. It doesn't mean I can't still enjoy life and want to go on living.

    When I was hiking the Inca trail, I met a couple in their 70s who were also hiking it. I met an Australian man in his mid-80s hiking in Italy. I want to be like those people.
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    Aug 15, 2008 3:27 PM GMT
    Chuy2010 saidId rather die at 70 than live until Im a 100yo anorexic twink.icon_rolleyes.gif

    I don't think the word "twink" would apply to any 100 year old. icon_lol.gif
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    Aug 15, 2008 3:39 PM GMT
    Global_Citizen said
    Chuy2010 saidId rather die at 70 than live until Im a 100yo anorexic twink.icon_rolleyes.gif

    I don't think the word "twink" would apply to any 100 year old. icon_lol.gif


    IDK...I've seen some pretty emaciated seniors.
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    Aug 15, 2008 3:46 PM GMT
    HighVoltageGuy said
    IDK...I've seen some pretty emaciated seniors.

    This is digressing from the topic, but this brings up the controversy about the definition of twink. To me, a twink isn't just a skinny guy. It's a young guy, smooth, with a cute face. And the "young" part of that is why I say no 100 year old could really be called a twink.