HEALTHY (LONG) LIVING: Scientists believe they have an idea of how caloric restriction diets lead to increaed longevity.
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Scientists have known for more than 70 years that the one surefire way to extend the lives of animals was to cut calories by an average of 30 to 40 percent. The question was: Why?
Now a new study begins to unravel the mystery and the mechanism by which reducing food intake protects cells against aging and age-related diseases.
Researchers report in the journal Cell that the phenomenon is likely linked to two enzymes—SIRT3 and SIRT4—in mitochondria (the cell's powerhouse that, among other tasks, converts nutrients to energy). They found that a cascade of reactions triggered by lower caloric intake raises the levels of these enzymes, leading to an increase in the strength and efficiency of the cellular batteries. By invigorating the mitochondria, SIRT3 and SIRT4 extend the life of cells, by preventing flagging mitochondria from developing tiny holes (or pores) in their membranes that allow proteins that trigger apoptosis, or cell death, to seep out into the rest of the cell.
"We didn't expect that the most important part of this pathway was in the mitochondria," says David Sinclair, an assistant professor of pathology at Harvard Medical School and a study co-author. "We think that we've possibly found regulators of aging."
In 2003 Sinclair's lab published a paper in Nature that described the discovery of a gene that switched on in the yeast cell in response to calorie restriction, which Sinclair calls a "master regulator in aging." Since then, his team has been searching for an analogous gene that plays a similar role in the mammalian cell.
The researchers determined from cultures of human embryonic kidney cells that lower caloric intake sends a signal that activates a gene inside cells that codes for the enzyme NAMPT (nicotinamide phosphoribosyltransferase). The two- to four-fold surge in NAMPT in turn triggers the production of a molecule called NAD (nicotinamide adenine dinucleotide), which plays a key role in cellular metabolism and signaling.
The uptick in NAD levels activates the SIRT3 and SIRT4 genes, increasing levels of their corresponding SIRT3 and SIRT4 enzymes, which then flood the interior of the mitochondria. Sinclair says he's not sure exactly how SIRT3 and SIRT4 beef up the mitochondria's energy output, but that events leading to cell death are at the very least delayed when there are vast quantities of the enzymes.
SIRT3 and SIRT4 are part of a family called sirtuins. (SIRT1, which helps extend cell life by modulating the number of repair proteins fixing DNA damage both inside and outside the cell's nucleus is also a member.) SIRT is short for sir-2 homologue—a well-studied protein that is known to extend yeast cell longevity. According to Sinclair, all of the mammalian SIRT genes (and their proteins) are possible drug targets for therapies aimed at extending life, as well as staving off age-related illnesses, such as Alzheimer's disease, cancers and metabolic disorders, like diabetes.
"I think SIRT3 is the next most interesting sirtuin from a drug development standpoint," Sinclair says. "It does protect cells, but there's growing evidence that it may mediate the benefits of exercise as well."
Sinclair's lab is now working on developing what he calls a possible "supermouse" with elevated levels of NAMPT to see if it lives longer and is more disease-resistant than normal mice.
Matt Kaeberlein, a pathologist at the University of Washington in Seattle, says that Sinclair's team has an interesting hypothesis connecting the mitochondria to longevity, but that it needs to be more directly tested in the context of dietary restriction. "If the NAMPT-overexpressing mice are long-lived and disease resistant, that will provide more support for this idea."
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5 Comments
Add CommentEating less probably increases our life span! In persons who are critically ill, it has now been shown that under-feeding such seriously sick patients will increase the chances of their survival! The mechanisms involved are probably more than one! And eating less has many other advantages than increasing the longivity!
Reply | Report Abuse | Link to thisi was wondering what do or can i eat for Eat (Less) to Live (Longer) issue i am 47 cant stop gaining weight ..high blood pressure .heart disease runs in family//the list goes on i would really like to start living i have 2 bad knees they just cripple me some days and full of arthitics would love to play with grand babies etc ..and my grandparents dies in their 60s
Reply | Report Abuse | Link to thisthank you connie fallon
sorry my typing is so messy and miss spelled i was upset while i was writing please help me
Reply | Report Abuse | Link to thisConnie, it's a long haul, but you can do it. You'll need some self-discipline. First, learn the difference between nutritious food and the foods you crave. A good clue is to eat things that are still living: carrots, apples, spinach, etc. and avoid things that are long dead: flour, milk, butter, cheese, etc. and religiously avoid industrial and fast "foods:" pizza, fried chicken, hamburgers, french fries, macaroni, etc. I'll bet money that the foods you love most are the worst for you. If you stop eating for flavor alone and don't use food for "comfort," that is eat when you're upset, you'll automatically begin to lose weight and regain your health. After awhile, six months to a year, you won't need discipline because your body will develop a taste for healthy eating. After that, it will be easy.
Reply | Report Abuse | Link to thisConnie, it's a long haul, but you can do it. You'll need some self-discipline. First, learn the difference between nutritious food and the foods you crave. A good clue is to eat things that are still living: carrots, apples, spinach, etc. and avoid things that are long dead: flour, milk, butter, cheese, etc. and religiously avoid industrial and fast "foods:" pizza, fried chicken, hamburgers, french fries, macaroni, etc. I'll bet money that the foods you love most are the worst for you. If you stop eating for flavor alone and don't use food for "comfort," that is eat when you're upset, you'll automatically begin to lose weight and regain your health. After awhile, six months to a year, you won't need discipline because your body will develop a taste for healthy eating. After that, it will be easy.
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