See also Negative calorie diet, very low calorie diet // In a negative calorie diet and several versions of this diet, ostensibly, dieters are to eat and drink food products that are nutritious but are said to have a negative caloric effect; , provide fewer food calories than the calories needed to digest them. ... Very low calorie diet (VLCD) is a diet with very or extremely low calorie consumption per day. ...

CRON redirects here. For the Unix command line cron, see crontab.

Calorie restriction or Caloric restriction (CR) is the practice of limiting dietary energy intake in the hope that it will improve health and retard aging. In human subjects, CR has been shown to lower cholesterol, fasting glucose, and blood pressure. Some consider these to be biomarkers of aging, since there is a correlation between these markers and risk of diseases associated with aging. Except for houseflies (below), animal species tested with CR so far, including primates, rats, mice, spiders, Drosophila, C. elegans and rotifers, have shown lifespan extension. CR is the only known dietary measure capable of extending maximum lifespan, as opposed to average lifespan. In CR, energy intake is minimized, but sufficient quantities of vitamins, minerals and other important nutrients must be eaten. To emphasize the difference between CR and mere "FR" (food restriction), CR is often referred to by a plethora of other names such as CRON or CRAN (calorie restriction with optimal/adequate nutrition), or the "high-low diet" (high in all nutrients aside from calories, in which it is "low"). Other names for the diet emphasize the goal of the diet, such as CRL (calorie restriction for longevity), or simply The Longevity Diet, as in a recently published book by that name. The crontab command, found in Unix and Unix-like operating systems, is used to schedule commands to be executed periodically. ... It has been suggested that Longevity genes be merged into this article or section. ... Cholesterol is a sterol (a combination steroid and alcohol), a lipid found in the cell membranes of all body tissues, and is transported in the blood plasma of all animals. ... A sphygmomanometer, a device used for measuring blood pressure. ... Biomarker is an occasionally used synonym for biosignature, which is a term used in astrobiology to indicate a measurable phenomenon that indicates the presence of life. ... Calorie restriction or Caloric restriction (CR) is the practice of limiting dietary energy intake in the hope that it will improve health and retard aging. ... Families 15, See classification A primate is any member of the biological order Primates, the group that contains all the species commonly related to the lemurs, monkeys, and apes, with the latter category including humans. ... Species 50 species; see text *Several subfamilies of Muroids include animals called rats. ... Mice may refer to: An abbreviation of Meetings, Incentives, Conferencing, Exhibitions. ... Diversity 111 families, 40,000 species Suborders Mesothelae Mygalomorphae Araneomorphae  See table of families Wikispecies has information related to: Spiders Spiders are predatory invertebrate animals that have two body segments, eight legs, no chewing mouth parts and no wings. ... Type Species Musca funebris Fabricius, 1787 Drosophila is a genus of small flies whose members are often called small fruit flies, or more appropriately vinegar flies, wine flies, pomace flies, grape flies, and picked fruit-flies. ... Binomial name Caenorhabditis elegans Maupas, 1900 Caenorhabditis elegans (IPA: ) is a free-living nematode (roundworm), about 1 mm in length, which lives in temperate soil environments. ... Classes Monogononta Digononta The rotifers make up a phylum of microscopic and near-microscopic pseudocoelomate animals. ... Maximum life span is a measure of the maximum number of years a member of a group can be expected to survive. ... Life expectancy is the average number of years remaining for a living being (or the average for a class of living beings) of a given age to live. ... Retinol (Vitamin A) For the record label, see Vitamin Records A vitamin is an organic compound required in tiny amounts for essential metabolic reactions in a living organism. ... A mineral is a naturally occurring substance formed through geological processes that has a characteristic chemical composition, a highly ordered atomic structure and specific physical properties. ... Link title {{portal|Food} A nutrient is either a chemical element or compound used in an organisms metabolism or physiology. ... Longevity is a term that generally refers to long life or great duration of life.[1] Reflections on longevity have usually gone beyond acknowledging the basic shortness of human life and have included thinking about methods to extend life. ...

Research history

In 1934, Clive McCay and Mary Crowell of Cornell University observed that laboratory rats fed a severely reduced calorie diet while maintaining vital nutrient 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 lifespan 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) (ISBN 0-398-05496-7). Year 1934 (MCMXXXIV) was a common year starting on Monday (link will display full 1934 calendar) of the Gregorian calendar. ... Cornell University is a university located in Ithaca, New York, USA. Its two medical campuses are in New York City and Education City, Qatar. ... Roy Lee Walford (June 29, 1924 - April 27, 2004) was an advocate of caloric restriction. ... Year 1986 (MCMLXXXVI) was a common year starting on Wednesday (link displays 1986 Gregorian calendar). ...

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 (see Roth et al below). In the meantime, many people have independently adopted the practice of calorie restriction in some form, hoping to achieve the expected benefits themselves. Among the most notable are the members of the Calorie Restriction Society. The Calorie Restriction Society is an organization composed of several thousand people practicing and studying Calorie restriction. ...

Trials were set up at Washington University in 2002 and involved about 30 participants. Dr. Luigi Fontana, clinical investigator, says CR practitioners seem to be ageing more slowly than the rest of us. "Take systolic blood pressure," he says. "Usually, that rises with age reliably, partly because the arteries are hardening. In my group, mean age is 55, and mean systolic blood pressure is 110: that’s at the level of a 20-year-old." Washington University in St. ... Blood pressure is the pressure exerted by the blood on the walls of the blood vessels. ... // Introduction Arteriosclerosis means the hardening of the arteries in Greek. ...

"Of course, I can’t tell you if my subjects will live to 130. So many uncontrollable factors affect length of life. I don’t have enough evidence to prove these people are ageing more slowly, but it looks like it."^[1]

A study conducted by the Salk Institute for Biological Studies, and published in the journal Nature in May 2007, determined that the gene PHA-4 is responsible for the longevity behind calorie restriction in animals, with similar results expected in humans.^[2] The discovery has given hope to the synthesising of future drugs to increase the human lifespan by simulating the effects of calorie restriction. However, MIT biologist Leonard Guarente cautioned that "(treatment) won't be a substitute for a healthy lifestyle. You'll still need to go to the gym,".^[3] Salk Institute Salk Institute The Salk Institute for Biological Studies is an independent non-profit educational research organization in La Jolla, California. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... This article does not cite any references or sources. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... For a non-technical introduction to the topic, see Introduction to Genetics. ... The Massachusetts Institute of Technology (MIT) is a private, coeducational research university located in Cambridge, Massachusetts. ... Leonard P. Guarente is an American biologist best known for his research on Life Span extension in Yeast. ...

Effects of CR on different organisms

Primates

Researchers at New York's Mount Sinai School of Medicine found that compared to monkeys fed a normal diet, squirrel monkeys on a life-long calorie-restrictive diet were less likely to develop Alzheimer's-like changes in their brains.^[4] Since squirrel monkeys are relatively long lived, definitive conclusions regarding whether or not they are aging slower are not yet available. A study on rhesus macaques was started in 1989 at the University of Wisconsin-Madison. Preliminary results show 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.^[5] Binomial name Macaca mulatta (Zimmermann, 1780) The Rhesus Macaque (Macaca mulatta), often called the Rhesus Monkey, is one of the best known species of Old World monkeys. ... The University of Wisconsin–Madison (also known as UW–Madison, Madison, Wisconsin, University of Wisconsin, or UW) is a highly selective public research university located in Madison, Wisconsin. ... Insulin sensitivity is the opposite of insulin resistance. ... Low-density lipoprotein (LDL) refers to a class and range of lipoprotein particles, varying somewhat in their size and contents, which carry cholesterol in the blood and around the body, for use by various cells. ... Atherosclerosis is a disease of arterial blood vessels. ...

Rats

Seventy years ago, McCay CM, et al., discovered that reducing the amount of calories fed to rats nearly doubled their lifespan. For the last seventy years, scientists have proposed hypotheses as to why. Some explanations included reduced cellular divisions, lower metabolism rates, and reduced production of free radicals generated by metabolism. Recently, Harvard professor David A. Sinclair has conducted research that provides a new explanation for the lifespan extension caused by calorie restriction. It involves the activation of a gene called Sirt1. When Sirt1 gene activity is increased by genetic manipulation, caloric restriction does not increase it any further. Knocking out the Sirt1 gene also eliminates any beneficial effect from caloric restriction. Resveratrol has been demonstrated to increase the activity of the Sirt1 gene the same way caloric restriction does.^{[citation needed]} When resveratrol increased the subject's lifespan, caloric restriction failed to increase it any further. This research was conducted in yeast and invertebrates, not in rats. Presently, Sirt1 gene activity has not been increased in rats by genetic manipulation. Look up Hypothesis in Wiktionary, the free dictionary. ... A few of the metabolic pathways in a cell. ... David Sinclair is a biologist best known for his research on the biology of lifespan extension and driving research towards treating diseases of aging. ... Sir2 is a family of closely related enzymes. ... Resveratrol is a phytoalexin produced by several plants. ...

Mice

Studies in female mice have shown that estrogen receptor-alpha declines in the pre-optic hypothalamus as they grow old. 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.^[6] Studies in female mice have shown that both Supraoptic nucleus (SON) and Paraventricular nucleus (PVN) lose about one-third of IGF-1R immunoreactive cells with normal aging. Also, Old caloricly restricted (CR) mice lost higher numbers of IGF-1R non-immunoreactive cells while maintaining similar counts of IGF-1R immunoreactive cells in comparison to Old-Al mice. Consequently, Old-CR mice show a higher percentage of IGF-1R immunoreactive cells reflecting increased hypothalamic sensitivity to IGF-1 in comparison to normally aging mice.^[7][8] The estrogen receptor is a receptor for estradiol (the main endogenous estrogen); it is located intracellularly, in parallel with other steroid hormone receptors. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... A human eye Eyes are organs of vision that detect light. ... The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. ... The paraventricular nucleus (PVN) is an aggregation of neurons in the hypothalamus, adjacent to the third ventricle. ...

Spider

Drosophila

Research in 2003 by Mair et al. ([8]) showed that calorie restriction has instantaneous effects on death rates in fruit flies of any age.

C. elegans

Rotifer

Why might CR increase longevity?

There have been many theories as to how CR works, and many of them have fallen out of favor or been disproved. These include reduced basal metabolic rate, developmental delay, the control animals being gluttons, and decreased glucocorticoid production. Basal metabolic rate (BMR) is the amount of energy expended while at rest in a neutrally temperate environment, in the post-absorptive state (meaning that the digestive system is inactive, which requires about twelve hours of fasting in humans). ... Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. ...

Hormesis hypothesis

A small, but rapidly growing number of researchers in the CR field are now proponents of a new theory known as the "Hormesis Hypothesis of CR". In the early 1940s, Southam & Ehrlich, 1943 reported that a bark extract that was known to inhibit fungal growth, actually stimulated growth when given at very low concentrations. They coined the term "hormesis" to describe such beneficial actions resulting from the response of an organism to a low-intensity biological stressor. The word "hormesis" is derived from the Greek word "hormaein" which means "to excite". A very low dose of a chemical agent may trigger from an organism the opposite response to a very high dose. ...

The Hormesis Hypothesis of CR proposes that the diet imposes a low-intensity biological stress on the organism, which elicits a defense response that helps protect it against the causes of aging. In other words, CR places the organism in a defensive state so that it can survive adversity, and this results in improved health and longer life. This switch to a defensive state may be controlled by longevity genes (see below). Longevity genes are genes that determine lifespan. ...

Recent research has suggested (see Matthias Bluher, C. Ronald Kahn, Barbara B. Kahn, et al.) that it is not reduced intake which influences longevity. This was done by studying animals which have their metabolism changed to reduce insulin uptake, consequently retaining the leanness of animals in the earlier studies. It was observed that these animals can have a normal dietary intake, but have a similarly increased lifespan. This suggests that lifespan is increased for an organism if it can remain lean and if it can avoid any excess accumulation of adipose tissue: if this can be done while not diminishing dietary intake (as in some minority eating patterns, see e.g. Living foods diet or Joel Fuhrman) then the 'starvation diet' anticipated as an impossible requirement by earlier researchers is no longer a precondition of increased longevity. Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is an anabolic polypeptide hormone that regulates carbohydrate metabolism. ... It has been suggested that Subcutaneous fat be merged into this article or section. ... The raw food diet (or living foods diet) is a dietary regimen consisting of uncooked and unprocessed organic foods. ... Dr. Joel Fuhrman, M.D. is a family medicine physician who practices in Flemington, New Jersey, USA. He specialises in treating some major illnesses through nutrition. ...

The extent to which these findings may apply to human nutrition and longevity is as noted above under investigation. A paper in the Proceedings of the National Academy of Sciences, U.S.A. in 2003 showed that practitioners of a CR diet had significantly better cardiovascular health (PMID 15096581). Also in progress are the development of CR mimetic interventions. The updated USDA food pyramid, published in 2005, is a general nutrition guide for recommended food consumption. ... Longevity is a term that generally refers to long life or great duration of life.[1] Reflections on longevity have usually gone beyond acknowledging the basic shortness of human life and have included thinking about methods to extend life. ... The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. ... A CR (Calorie Restriction) mimetic is a particular compound or molecule that may -- if successful -- enable organisms to derive many of the health and life-extending benefits noted in calorically restricted diets. ...

Sir2/SIRT1

Sir2 or "silent information regulator 2" is a longevity gene in baker's yeast cells that extends lifespan by suppressing DNA instability (see Sinclair and Guarente, Cell, 1997).^[9] In mammals Sir2 is known as SIRT1. Recent discoveries have suggested that the gene Sir2 might underlie the effect of CR. In baker's yeast the Sir2 enzyme is activated by CR, which leads to a 30% lifespan extension. David Sinclair at Harvard Medical School, Boston, showed that in mammals the SIRT1 gene is turned on by a CR diet, and this protects cells from dying under stress.^[10] An article in the June 2004 issue of the journal Nature showed that SIRT1 releases fat from storage cells.^[11] See also SIRT1 in the Ensembl genome browser. Sinclair's lab reported that they have found small molecules (e.g. resveratrol) that activate Sir2/SIRT1 and extend the lifespan of yeast,^[12] nematode worms, fruit flies,^[13] and mice consuming a high caloric diet.^[14] An Italian group headed by Antonio Cellerino showed that resveratrol extends the lifespan of a vertebrate fish by 59%.^[15] In the yeast, worm, and fly studies, resveratrol did not extend lifespan if the Sir2 gene was mutated. A group of researchers headed by Matthew Kaeberlein and Brian Kennedy at the University of Washington Seattle believe that Sinclair's work on resveratrol is an artifact and that the Sir2 gene has no relevance to CR.^[16] Sir2 is a family of closely related enzymes. ... For a non-technical introduction to the topic, see Introduction to Genetics. ... Sir2 (whose homology in mammals is SIRT1, SIR2L1 or Sir2α) is a member of a family of closely related enzymes, the sirtuins. ... Binomial name Saccharomyces cerevisiae Saccharomyces cerevisiae is a species of budding yeast. ... Sir2 is a family of closely related enzymes. ... Nature is one of the most prominent scientific journals, first published on 4 November 1869. ... Resveratrol is a phytoalexin produced by several plants. ...

DHEA

While calorie restriction has been shown to increase DHEA in primates (PMID 12543259), it has not been shown to increase DHEA in post-pubescent primates (PMID 15247063). Dehydroepiandrosterone (DHEA) is a natural steroid hormone produced from cholesterol by the adrenal glands. ... Dehydroepiandrosterone (DHEA) is a natural steroid hormone produced from cholesterol by the adrenal glands. ...

Free radicals and glycation

Two very prominent theories of aging are the free radical theory and the glycation theory, both of which can explain how CR could work. With high amounts of energy available, mitochondria do not operate very efficiently and generate more superoxide. With CR, energy is conserved and there is less free radical generation. A CR organism will be less fat and require less energy to support the weight, which also means that there does not need to be as much glucose in the bloodstream. Less blood glucose means less glycation of adjacent proteins and less fat to oxidize in the bloodstream to cause sticky blocks resulting in atherosclerosis. Type II Diabetics are people with insulin insensitivity caused by long-term exposure to high blood glucose. Obesity leads to type 2 diabetes. Type 2 diabetes and uncontrolled type 1 diabetes are much like "accelerated aging", due to the above effects. There may even be a continuum between CR and the metabolic syndrome. The free-radical theory of aging (FRTA) is that organisms age because protein, lipid and nucleic acids (DNA, RNA) accumulate free radical damage with the passage of time. ... Glycation is the result of a sugar-reducing molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... Lewis electron configuration of superoxide. ... Glycation is the result of a sugar-reducing molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... Metabolic syndrome is a combination of medical disorders that increase ones risk for cardiovascular disease and diabetes. ...

In examining Calorie Restriction with Optimal Nutrition, it is observed that with less food, and equal nutritional value, there is a higher ratio of nutrients to calories. This may lead to more ideal essential and beneficial nutrient levels in the body. Many nutrients can exist in excess to their need, without side effects as long as they are in balance and not beyond the body's ability to store and circulate them. Many nutrients serve protective effects as antioxidants, and will be at higher levels in the body as there will be lower levels of free radicals due to the lower food intake. An antioxidant is a chemical that prevents the oxidation of other chemicals. ...

Calorie Restriction with Optimal Nutrition has not been tested in comparison to Calorie Excess with Optimal Nutrition. It may be that with extra calories, nutrition must be similarly increased to ratios comparable to that of Calorie Restriction to provide similar antiaging benefits.

Stated levels of calorie needs may be biased towards sedentary individuals. Calorie restriction may be more of adapting the diet to the body's needs.

Although aging can be conceptualized as the accumulation of damage, the more recent determination that free radicals participate in intracellular signaling has made the categorical equation of their effects with "damage" more problematic than was commonly appreciated in years past.

Papers on CR in yeast: dismissing increased respiration

In late 2005 Matt Kaeberlein and Brian Kennedy published two important papers on calorie restriction in yeast. In the first, they show that calorie restriction does not increase respiration in yeast (in contrast with the model proposed by Lenny Guarente). In the second, calorie restriction decreased the activity of TOR, a nutrient-responsive signaling protein already known to regulate aging in worms and flies. This paper is the first to directly link TOR to calorie restriction. There have been several notable people named Brian Kennedy: Brian Kennedy, a gay journalist and activist who helped set up the London Lesbian and Gay Centre in 1985. ...

Evolution

It has been recently argued that during years of famine, it may be evolutionarily desirable for an organism to avoid reproduction but to uprate protective and repair enzyme mechanisms to try to ensure that it is fit for reproduction the following years. This seems to be supported by recent work studying hormones.^[17]

Objections to Calorie Restriction

No benefit to houseflies

One of the most significant oppositions to caloric restriction comes from Michael Cooper, who has shown that caloric restriction has no benefit in the housefly.^[18] Michael Cooper claims that the widely purported effects of calorie restriction may be because a diet containing more calories can increase bacterial proliferation, or that the type of high calorie diets used in past experiments have a stickiness, general composition, or texture that reduces longevity. Binomial name Linnaeus, 1758 The housefly (also house fly or house-fly), Musca domestica, is the most common fly occurring in homes, the most familiar of all flies and indeed one of the most widely distributed animals; it is a pest that can carry and transmit serious diseases. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ...

Catabolic damage

A major conflict with calorie restriction is that a calorie excess is needed to prevent catabolizing the body's tissues.^{[citation needed]} A body in a catabolic state promotes the degeneration of muscle tissue, including the heart. Anabolism is the aspect of metabolism that contributes to growth. ...

Physical activity testing biases

While some tests of calorie restriction have shown increased muscle tissue in the calorie-restricted test subjects,^{[citation needed]} how this has occurred is unknown.^{[citation needed]} Muscle tissue grows when stimulated, so it is possible that the calorie-restricted test animals exercised more than their companions on higher calories. The reasons behind this may be that animals enter a foraging state during calorie restriction. Such tests need to be monitored to make sure that levels of physical activity are equal between groups.^{[citation needed]}

Insufficient calories and amino acids for exercise

Exercise has also been shown to increase health and lifespan and lower the incidence of several diseases. Calorie restriction comes into conflict with the high calorie needs of athletes, and may not provide them adequate levels of energy or sufficient amino acids for repair, although this is not a criticism of CR per se, since it is certainly possible to be an unhealthy athlete, or an athlete destined to die at a young age due to poor diet, stresses, etc. Look up athlete in Wiktionary, the free dictionary. ...

Benefits only the young

There is evidence to suggest that the benefit of CR in rats might only be reaped in early years. A study on rats which were gradually introduced to a CR lifestyle at 18 months showed no improvement over the average lifespan of the Ad libitum group.^[19] This view, however, is disputed by Spindler, Dhahbi, and colleagues who showed that in late adulthood, acute CR partially or completely reversed age-related alterations of liver, brain and heart proteins and that mice placed on CR at 19 months of age show increases in lifespan.^[20] Ad libitum is Latin for at ones pleasure, often shortened to Ad lib. ...

Possible contraindications

Both animal and human research suggest CR may be contraindicated for people with amyotrophic lateral sclerosis (ALS). Research on a transgenic mouse model of ALS demonstrates that CR may hasten the onset of death in ALS. Hamadeh et al therefore concluded: "These results suggest that CR diet is not a protective strategy for patients with amyotrophic lateral sclerosis (ALS) and hence is contraindicated."^[21] Hamadeh et al also note two human studies^[22][23] that they indicate show "low energy intake correlates with death in people with ALS." However, in the first study, Slowie, Paige, and Antel state: "The reduction in energy intake by ALS patients did not correlate with the proximity of death but rather was a consistent aspect of the illness." They go on to conclude: "We conclude that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake." (PMID 8604660) Amyotrophic lateral sclerosis (ALS, sometimes called Lou Gehrigs Disease, Maladie de Charcot or motor neurone disease) is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. ... A genetically modified organism (GMO) is an organism whose genetic material has been altered using the genetic engineering techniques generally known as recombinant DNA technology. ...

Previously, Pedersen and Mattson also found that in the ALS mouse model, CR "accelerates the clinical course" of the disease and had no benefits.^[24] Suggesting that a calorically dense diet may slow ALS, a ketogenic diet in the ALS mouse model has been shown to slow the progress of disease.^[25] More recently, Mattson et al opine that the death by ALS of Roy Walford, a pioneer in CR research and its antiaging effects, may have been a result of his own practice of CR.^[26] However, as Mattson et al acknowledge, Walford's single case is an anecdote that by itself is insufficient to establish the proposed cause-effect relation. The ketogenic diet is a very high fat diet that relies on inducing a state of ketosis. ... Roy Lee Walford (June 29, 1924 - April 27, 2004) was an advocate of caloric restriction. ... Anecdotal evidence is an informal account of evidence in the form of an anecdote, or hearsay. ...

Negligible effect on larger organisms

Another objection to CR as an advisable lifestyle for humans is the claim that the physiological mechanisms that determine longevity are very complex, and that the effect would be small to negligible in our species.^[27]

Intermittent fasting as an alternative approach

Studies by Mark P. Mattson, Ph. D., chief of the National Institute on Aging's (NIA) Laboratory of Neurosciences, and colleagues have found that intermittent fasting and calorie restriction affect the progression of diseases similar to Huntington's disease, Parkinson's disease, and Alzheimer's disease in mice (PMID 11119686). In one study, rats and mice ate a low-calorie diet or were deprived of food for 24 hours every other day (PMID 12724520). Both methods improved glucose metabolism, increased insulin sensitivity, and increased stress resistance. Researchers have long been aware that calorie restriction extends lifespan, but this study showed that improved glucose metabolism also protects neurons in experimental models of Parkinson's and stroke. The National Institute on Aging is a division of the National Institutes of Health, located in Bethesda,_Maryland. ... Insulin sensitivity is the opposite of insulin resistance. ... In medical terms, stress is the disruption of homeostasis through physical or psychological stimuli. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... Stroke (or cerebrovascular accident or CVA) is the clinical designation for a rapidly developing loss of brain function due to an interruption in the blood supply to all or part of the brain. ...

Another NIA study found that intermittent fasting and calorie restriction delays the onset of Huntington's disease-like symptoms in mice and prolongs their lives (PMID 12589027). Huntington's disease (HD), a genetic disorder, results from neuronal degeneration in the striatum. This neurodegeneration results in difficulties with movements that include walking, speaking, eating, and swallowing. People with Huntington's also exhibit an abnormal, diabetes-like metabolism that causes them to lose weight progressively. A genetic disorder is a disease caused by abnormalities in genes or chromosomes. ... Coronal slices of human brain showing the basal ganglia, the striatum and pallidum globus pallidus: external segment (GPe), subthalamic nucleus (STN), globus pallidus: internal segment (GPi), and substantia nigra (SN). ...

This NIA study compared adult HD mice who ate as much as they wanted to HD mice who were kept on an intermittent fasting diet during adulthood. HD mice possess the abnormal human gene huntingtin and exhibit clinical signs of the disease, including abnormal metabolism and neurodegeneration in the striatum. The mice on the fasting program developed clinical signs of the disease about 12 days later and lived 10 to 15% longer than the free-fed mice. The brains of the fasting mice also showed less degeneration. Those on the fasting program also regulated their glucose levels better and did not lose weight as quickly as the other mice. Researchers found that fasting mice had higher brain-derived neurotrophic factor (BDNF) levels. BDNF protects neurons and stimulates their growth. Fasting mice also had high levels of heat-shock protein-70 (Hsp70), which increases cellular resistance to stress. Brain-derived neurotrophic factor (BDNF) is exactly as it states; a neurotrophic factor usually derived in the brain. ... Hsp70 is a family of heat shock proteins including HSP70 (also known as Hsp72), Bip and the prokaryotic protein DnaK with an approximate molecular weight of 70 kDa. ...

Another NIA study compared intermittent fasting with cutting calorie intake. Researchers let a control group of mice eat freely (ad libitum). Another group was fed 60% of the calories that the control group consumed. A third group was fasted for 24 hours, then permitted to free-feed. The fasting mice didn't cut total calories at the beginning and the end of the observation period, and only slightly cut calories inbetween. A fourth group was fed the average daily intake of the fasting mice every day. Both the fasting mice and those on a restricted diet had significantly lower blood sugar and insulin levels than the free-fed controls. Kainic acid, a toxin that damages neurons, was injected into the dorsal hippocampus of all mice. Hippocampal damage is associated with Alzheimer's. Interestingly, the scientists found less damage in the brains of the fasting mice than in those that ate a restricted diet, and most damage in mice with an unrestricted diet. But the control group which ate the average daily intake of the fasting mice also showed less damage than the mice with restricted diet.^[28] Kainic acid is an acid present in some algae. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... The hippocampus is structurally located inside the medial temporal lobe of the brain. ...

Another Mattson study^[29] in which overweight adult asthmatics followed alternate day calorie restriction (ADCR) for eight weeks showed marked improvement in oxidative stress, inflammation, and severity of the disease. Evidence from the medical literature suggests that ADCR in the absence of weight loss prolongs lifespan in humans^[30].

See also

• Alzheimer's disease
• Anorexia nervosa
• Calorie Restriction Society
• Fasting
• Huntington's disease
• Life extension
• Orthorexia
• Resveratrol
• Starvation

For the symphonic black metal band, see Anorexia Nervosa (band) For other uses, see Anorexia Anorexia nervosa is a psychiatric diagnosis that describes an eating disorder characterized by low body weight and body image distortion with an obsessive fear of gaining weight. ... The Calorie Restriction Society is an organization composed of several thousand people practicing and studying Calorie restriction. ... Fasting is primarily the act of willingly abstaining from some or all food, drink, or both, for a period of time. ... Life extension refers to an increase in maximum or average lifespan, especially in humans, by slowing down or reversing the processes of aging. ... Orthorexia, or orthorexia nervosa in full, is closely related to the disorder anorexia nervosa. ... Resveratrol is a phytoalexin produced by several plants. ... A female child during the Nigerian-Biafran war of the late 1960s, shown suffering the effects of severe hunger and malnutrition. ...

Notes

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 163rd day of the year (164th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 123rd day of the year (124th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 123rd day of the year (124th in leap years) in the Gregorian calendar. ...

References

• Genes & Development ; Koubova, J; 17(3):313-321 (2003) Review of maximum life span extension by calorie restriction

• The Retardation of Aging and Disease by Dietary Restriction Richard Weindruch, Roy L. Walford (1988). ISBN 0-398-05496-7

• Ageless Quest. Lenny Guarente, Cold Spring Harbor Press, NY. 2003. ISBN 0-87969-652-4.

• The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. Journal of Nutrition, 116(4), pages 641-54.Weindruch R, et al.,April, 1986. PMID 3958810.

• Caloric Restriction and Aging Richard Weindruch in Scientific American, Vol. 274, No. 1, pages 46--52; January 1996.

• 2-Deoxy-D-Glucose Feeding in Rats Mimics Physiological Effects of Caloric Restriction. Mark A. Lane, George S. Roth and Donald K. Ingram in Journal of Anti-Aging Medicine, Vol. 1, No. 4, pages 327--337; Winter 1998.

• Biomarkers of caloric restriction may predict longevity in humans. Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ.: 297: 811, Science 2002. PMID 12161648.

• Eat more, weigh less, live longer, New Scientist, January 2003. http://www.newscientist.com/article.ns?id=dn3303

• Extended longevity in mice lacking the insulin receptor in adipose tissue. Bluher, Khan BP, Kahn CR, Science 299(5606): 572-4, 24 January 2003. PMID 12543978.

• Interview, "I want to live forever", Cynthia Kenyon, Professor of Biochemistry and Biophysics at the University of California, San Francisco, by James Kingsland. New Scientist online, 20 October 2003. http://www.newscientist.com/channel/opinion/mg18024175.300

• Sir2-independent life span extension by calorie restriction in yeast, Kaeberlein, M., K.T. Kirkland, S. Fields, and B.K. Kennedy. 2004. PLoS Biol 2: E296. PMID 15328540.

• Substrate-specific Activation of Sirtuins by Resveratrol, Kaeberlein, M., T. McDonagh, B. Heltweg, J. Hixon, E.A. Westman, S.D. Caldwell, A. Napper, R. Curtis, P.S. Distefano, S. Fields, A. Bedalov, and B.K. Kennedy. 2005. J Biol Chem 280: 17038-45. PMID 15684413.

• Interview, Longevity and Genetics, Matt Kaeberlein, Brian Kennedy. SAGE Crossroads

• Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast, Kaeberlein M, Hu D, Kerr EO, Tsuchiya M, Westman EA, Dang N, Fields S, Kennedy BK. PLoS Genet. 25 November 2005;1(5):e69

• Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients, Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK. Science. 18 November 2005;310(5751):1193-6.

• PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans, Siler H. Panowski, Suzanne Wolff, Hugo Aguilaniu, Jenni Durieux & Andrew Dillin. 2 May 2007. Nature advance online publication | doi:10.1038/nature05837

• Fasting fosters longevity in rats. Science News, Vol. 116, No. 22: 375, 1 December 1979.

is the 24th day of the year in the Gregorian calendar. ... Year 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... Cynthia Kenyon (c. ... October 20 is the 293rd day of the year (294th in leap years) in the Gregorian calendar. ... Year 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... is the 329th day of the year (330th in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... is the 322nd day of the year (323rd in leap years) in the Gregorian calendar. ... Year 2005 (MMV) was a common year starting on Saturday (link displays full calendar) of the Gregorian calendar. ... Science News is an American weekly magazine devoted to short articles about new scientific and technical developments, typically gleaned from recent scientific and technical journals. ... is the 335th day of the year (336th in leap years) in the Gregorian calendar. ... Also: 1979 by Smashing Pumpkins. ...

External links

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• Calorie Restriction Society
• Calorie Restriction with Optimum Nutrition Web site.
• Mechanisms of Aging.

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Articles

• Calorie Restricters Seem Young at Heart
• American Scientist Online, "Aging: A Biological Perspective" retrieved September 29, 2005
• Life Extension, Caloric Restriction and Scientific Philanthropy
• Diet your way to a long, miserable life!
• Scientists Have Found the Gene That Decides How Long We Live
• The Fast Supper
• Calorie Restriction