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    Calorie Restriction and Longevity
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    Calorie Restriction and Longevity Experiments and Research

    • Calorie Restriction Explained [View Experiment]
    • Calorie Restriction Calculator [View Experiment]
    • Caloric restriction improves memory in elderly humans [View Experiment]
    • Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans [View Experiment]
    • Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study [View Experiment]
    • Can experiments on caloric restriction be reconciled with the disposable soma theory for the evolution of senescence? [View Experiment]
    • Caloric restriction [View Experiment]
    • Calorie Source, Calorie Restriction, Immunity and Aging of Mice [View Experiment]
    • Researchers discover first gene that specifically links calorie restriction to longevity [View Experiment]
    • Caloric Restriction for Longevity: Paradigm, Protocols and Physiological Findings in Animal Research [View Experiment]
    • Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration [View Experiment]
    • Calorie restriction and aging: review of the literature and implications for studies in humans [View Experiment]
    • The Role of Oxidative Stress in Relation to Caloric Restriction and Longevity [View Experiment]
    Calorie Restriction and Longevity Background

    Definition

    Caloric restriction (CR), or calorie restriction, without malnutrition, is a dietary regimen that restricts calorie intake, where the baseline for the restriction varies, usually being the previous, unrestricted, intake of the subjects.

    Calorie Restriction and Longevity

    Calorie restriction without malnutrition has been shown to improve age-related health and to slow the aging process in a wide range of animals and some fungi.

    CR is one of the few dietary interventions that have been documented to increase both the median and maximum lifespan in a variety of species, among them yeast, fish, rodents and dogs. There are currently ongoing studies to investigate whether CR works in nonhuman primates, and its effects on human health and metabolic parameters associated with CR in other species. The results so far are positive, but the studies are not yet complete, due to the long lifespan of the species.

    Calorie restriction is a feature of several dietary regimens, including the Okinawa diet and the CRON-diet.

    In 1934, Mary Crowell and Clive McCay of Cornell University observed that laboratory rats fed a severely reduced calorie diet while maintaining micronutrient levels resulted in life spans of up to twice as long as otherwise expected. These findings were explored in detail by a series of experiments with mice conducted by Roy Walford and his student Richard Weindruch. In 1986, Weindruch reported that restricting the calorie intake of laboratory mice proportionally increased their life span compared to a group of mice with a normal diet. The calorie-restricted mice also maintained youthful appearances and activity levels longer and showed delays in age-related diseases. The results of the many experiments by Walford and Weindruch were summarized in their book The Retardation of Aging and Disease by Dietary Restriction (1988)

    The findings have since been accepted and generalized to a range of other animals. Researchers are investigating the possibility of parallel physiological links in humans. In the meantime, many people have independently adopted the practice of calorie restriction in some form.

    Some research has shown CR to reduce atherosclerosis risk factors.

    A small study of long-term CR practitioners studied the effects of a diet with 10-25% less calorie intake than the average "Western" diet. Mean Body mass index (BMI) was 19.6 in the CR group; the matched group BMI was 25.9, comparable to the BMI for middle-aged people in the US.

    The mean BMI in the CR group dropped from 24 (range of 19.4 to 29.6) to 19.5 (range of 16.5 to 22.8) over periods of 3–15 years. Nearly all the decrease in both BMI and cardiovascular risk factors occurred in the first year. Adjusting for age, the average total cholesterol and LDL (bad) cholesterol levels in the CR group were below those seen in all but the lowest 10% of the population. The average HDL (good) cholesterol levels were in the 85th to 90th percentile range for normal middle-aged US men.

    A 2009 research paper showed that a calorie restricted diet can improve memory in normal to overweight elderly. The diet also resulted in decreased insulin levels and reduced signs of inflammation. Scientists believe that memory improvement in this experiment was caused by the lower insulin levels, because high insulin levels are usually associated with lower memory and cognitive function. However, that relation seems to be age-specific since another study, when analyzing people older than 65, those who were underweight had a higher dementia risk than normal or overweight people.

    Although most studies conducted showed that these diets can improve longevity and health in the long term, the effects of calorie restriction on humans is still controversial. Some studies on humans revealed a number of benefits of calorie restriction but also major side effects such as loss of muscle mass, muscle strength and loss of bone. In the middle aged or elderly low body weight is associated with premature mortality from cardiovascular disease and cancers. Confounds to these studies exist but higher mortality rates make the view that human CR leads to increases in lifespan as robust as CR leads to in rodents questionable nonetheless. An expert on aging has voiced concern over his CR practicing colleague Mark Mattson saying "This guy has no reserves."

    The health concerns in the case of calorie restriction begin when an individual cuts off too many calories. Researchers have reported that "excessive calorie restriction causes malnutrition and can lead to anemia, muscle wasting, weakness, dizziness, lethargy, fatigue, nausea, diarrhea, constipation, gallstones, irritability and depression". Although calorie restriction may have potential benefits for individuals, the majority of nutritionists agree that a diet that does not comprise enough calories for the individual's body may lead to serious health problems.

    By persistently consuming fewer calories than the body needs to maintain itself, an individual can become underweight. One study has shown that having a BMI lower than 18, for women, is associated with significantly increased mortality from noncancer, non−cardiovascular disease causes. The results were the same when not accounting for those who were underweight because they might have been already sick or were smokers. However, the study focused solely on BMI and did not look specifically at diet.

    A study on rhesus macaques, funded by the National Institute on Aging, was started in 1989 at the University of Wisconsin–Madison and is still ongoing. This study has so far shown that caloric restriction in rhesus monkeys blunts aging and significantly delays the onset of age related disorders such as cancer, diabetes, cardiovascular disease and brain atrophy. The monkeys were enrolled in the study at ages of between 7 and 14 years; at the 20 year point 80% of the calorically restricted monkeys were still alive, compared to only half of the controls. These results bore out earlier preliminary results that showed lower fasting insulin and glucose levels as well as higher insulin sensitivity and LDL profiles associated with lower risk of atherogenesis in dietary restricted animals.

    Seventy years ago, McCay CM, et al., discovered that reducing the amount of calories fed to rodents nearly doubled their lifespans. The life extension was varied for each species but on average, there was a 30-40% increase in lifespan in both mice and rats. CR preserves a range of structural and functional parameters in aging rodents. For example, studies in female mice have shown that estrogen receptor-alpha declines in the aging pre-optic hypothalamus. The female mice that were given a calorically restricted diet during the majority of their lives maintained higher levels of ERα in the pre-optic hypothalamus than their non-calorically restricted counterparts.

    Fungi model are very easy to manipulate and many crucial steps toward the understanding of aging has been done with it. Many studies were published in budding yeast and fission yeast to analyse the cellular mechanisms behind the increased longevity due to calorie restriction. First, calorie restriction is often called dietary restriction because the same effects on life span can be reached by only changing the nutrient quality without changing the amount of calories. The data from Dr Guarente, Dr Kennedy, Dr Jazwinski, Dr Kaeberlein, Dr Longo, Dr Shadel, Dr Nyström, Dr Piper and others showed that genetic manipulations in nutrient signaling pathways could mimic the effects of dietary restriction. In some case dietary restriction needs mitochondrial respiration to increase longevity (chronological aging) and in some other case not (replicative aging). Nutrient sensing in yeast controls stress defense, mitochondrial functions, Sir2 and others.

    Research in 2003 by Mair et al. showed that calorie restriction extends the life of fruit flies (Drosophila) of any age with instantaneous effects on death rates.

    For more information: http://en.wikipedia.org/wiki/Calorie_restriction

    Source: Wikipedia (All text is available under the terms of the GNU Free Documentation License and Creative Commons Attribution-ShareAlike License.)

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