Calorie restriction, caloric restriction, or energy restriction, is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. "Reduce" can be defined relative to the subject's previous intake before intentionally restricting calories, or relative to an average person of similar body type. Commonly consumed food components containing calories are carbohydrates, proteins and fat.
In preliminary research, some non-human species on calorie restriction diets without malnutrition may exhibit slowing of the biological aging process, resulting in an increase in both median and maximum lifespan, but this effect is not universal. In humans, the long-term health effects of moderate caloric restriction with sufficient nutrients are unknown.
Risks of malnutritionEdit
The term "calorie restriction" as used in the study of aging refers to dietary regimens that reduce calorie intake without incurring malnutrition. If a restricted diet is not designed to include essential nutrients, malnutrition may result in serious deleterious effects, as shown in the Minnesota Starvation Experiment. This study was conducted during World War II on a group of lean men, who restricted their calorie intake by 45% for 6 months and composed roughly 77% of their diet with carbohydrates. As expected, this malnutrition resulted in many positive metabolic adaptations (e.g. decreased body fat, blood pressure, improved lipid profile, low serum T3 concentration, and decreased resting heart rate and whole-body resting energy expenditure), but also caused a wide range of negative effects, such as anemia, edema, muscle wasting, weakness, neurological deficits, dizziness, irritability, lethargy, and depression.
Short-term studies in humans report a loss of muscle mass and strength and reduced bone mineral density. However, whether or not the reduction in bone mineral density actually harms bone health is unclear. In a study in premenopausal women, bone mineral density after weight loss was higher when normalized for body weight; reduced bone mineral density is also observed in humans undergoing long-term calorie restriction with adequate nutrition, but no fractures have been reported and the reduction in bone mineral density was not associated with deleterious changes in bone microarchitecture.
The authors of a 2007 review of the caloric restriction literature warned that "it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat."
Lower-than-normal body mass index, high mortalityEdit
Caloric restriction diets typically lead to reduced body weight, yet reduced weight can come from other causes and is not in itself necessarily healthy. In some studies, low body weight has been associated with increased mortality, particularly in late middle-aged or elderly subjects. Low body weight in the elderly can be caused by pathological conditions associated with aging and predisposing to higher mortality (such as cancer, chronic obstructive pulmonary disorder, or depression) or of the cachexia (wasting syndrome) and sarcopenia (loss of muscle mass, structure, and function). One study linked a body mass index lower than 18 in women with increased mortality from noncancer, non−cardiovascular disease causes. The authors attempted to adjust for confounding factors (cigarette smoking, failure to exclude pre-existing disease); others argued that the adjustments were inadequate.
- "epidemiologists from the ACS (American Cancer Society), American Heart Association, Harvard School of Public Health, and other organizations raised specific methodologic questions about the recent Centers for Disease Control and Prevention study and presented analyses of other data sets. The main concern ... is that it did not adequately account for weight loss from serious illnesses such as cancer and heart disease ... [and] failed to account adequately for the effect of smoking on weight ... As a result, the Flegal study underestimated the risks from obesity and overestimated the risks of leanness."
Such epidemiological studies of body weight are not about caloric restriction as used in anti-aging studies; they are not about caloric intake to begin with, as body weight is influenced by many factors other than energy intake, Moreover, "the quality of the diets consumed by the low-body mass index individuals are difficult to assess, and may lack nutrients important to longevity." Typical low-calorie diets rarely provide the high nutrient intakes that are a necessary feature of an anti-aging calorie restriction diet. As well, "The lower-weight individuals in the studies are not a caloric restriction because their caloric intake reflects their individual ad libitum set-points and not a reduction from that set-point."
Triggering binge eatingEdit
Young or pregnantEdit
Long-term caloric restriction at a level sufficient for slowing the aging process is generally not recommended in children, adolescents, and young adults (under the age of approximately 21), because this type of diet may interfere with natural physical growth, as has been observed in laboratory animals. In addition, mental development and physical changes to the brain take place in late adolescence and early adulthood that could be negatively affected by severe caloric restriction. Pregnant women and women trying to become pregnant are advised not to practice calorie restriction, because low BMI may result in ovulatory dysfunction (infertility), and underweight mothers are more prone to preterm delivery.
Even though there has been research on caloric restriction for over 70 years, the mechanism by which caloric restriction works is not well understood. Some explanations include reduced core body temperature, reduced cellular divisions and lower metabolic rate, according to one review of laboratory research.
Caloric restriction lowers the core body temperature, a phenomenon believed to be an adaptive response to reduce energy expenditure when nutrients availability is limited. Lowering the temperature may prolong the lifespan of cold blooded animals. Mice, which are warm blooded, have been engineered to have a reduced core body temperature which increased the lifespan independently of calorie restriction.
It has been recently argued that during years of famine, it may be evolutionarily desirable for an organism to avoid reproduction and to up-regulate protective and repair enzyme mechanisms to ensure that it is fit for reproduction in future years. This argument seems to be supported by recent work studying hormones. Prolonged severe CR lowers total serum and free testosterone while increasing sex hormone binding globulin concentrations in humans; these effects are independent of adiposity.
Lowering of the concentration of insulin and substances related to insulin, such as insulin-like growth factor 1 and growth hormone, has been shown to up-regulate autophagy, the repair mechanism of the cell. A related hypothesis suggests that caloric restriction works by decreasing insulin levels and thereby up-regulating autophagy, but caloric restriction affects many other health indicators, and it is still undecided whether insulin is the main concern. Calorie restriction has been shown to increase DHEA in primates, but it has not been shown to increase DHEA in post-pubescent primates. The extent to which these findings apply to humans is still under investigation.
Ancient medicine, the province of Hippocrates and Galen after him, taught that the very fat were destined to die suddenly more often than the slender. Around AD 1000 Avicenna taught the elderly to eat less than when they were young. Around 1500 because his health was failing due to gluttony, the Venetian nobleman Luigi Cornaro adopted a calorie restricted diet at age 35 and went on to live to be 102 years old. His very successful book Discorsi della vita sobria described his regimen, restricting himself to 350 g (12 oz) of food daily (including bread, egg yolk, meat, and soup) and 410 ml (14 US fl oz) of wine.
In 1919 after observing starvation in Central Europe during World War I, Francis Benedict and his colleagues published Human Vitality and Efficiency Under Prolonged Restricted Diet based on their experiment with 10% calorie reduction on male college students at the Carnegie Institution for Science. Reduced rations had turned out to be "not necessarily cataclysmic." Faced with some evidence for what was unknown at the time but today is called metabolic adaptation, Benedict wanted to find the science behind what appeared to be an adjustment in metabolic rate when food intake was below energy expenditure.
Hoping to learn how to refeed the people who had starved during World War II, between 1944 and 1945, 36 healthy conscientious objectors participated in the Minnesota Starvation Experiment, published in 1950 as The Biology of Human Starvation by lead investigator Ancel Keys and colleagues. Because the men were receiving 40% CR and subject to malnutrition this study was not one of calorie restriction per se.[nb 1]
EA Vallejo published a study of approximately 35% CR in the Spanish language in 1957, testing CR without malnutrition in nonobese elderly persons. About 30% CR for six months was achieved accidentally in the Biosphere 2 experiment during the 1990s.
In the 2000s, the US National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases mounted the CALERIE clinical trials with goals of 20%, 25% and 30% CR at three sites for six months to a year in Phase 1 and for two years in Phase 2.
Studies have been conducted to examine the effects of calorie restriction with adequate intake of nutrients in humans; however, long-term effects are unknown. One objection to calorie restriction in humans is a claim that the physiological mechanisms determining longevity are complex, and that the effect would be small to negligible. Effects of calorie restriction in humans over multiple years or decades may be small in comparison to conventional medical and public health interventions, but have not yet been clearly determined.
In a 2017 collaborative report on rhesus monkeys by scientists of the US National Institute on Aging and the University of Wisconsin, caloric restriction in the presence of adequate nutrition was effective in delaying the effects of aging. Older age of onset, female sex, lower body weight and fat mass, reduced food intake, diet quality, and lower fasting blood glucose levels were factors associated with fewer disorders of aging and with improved survival rates. Specifically, reduced food intake was beneficial in adult and older primates, but not in younger monkeys. The study indicated that caloric restriction provided health benefits with fewer age-related disorders in elderly monkeys and, because rhesus monkeys are genetically similar to humans, the benefits and mechanisms of caloric restriction may apply to human health during aging.
It has been known since the 1930s that reducing the number of calories fed to laboratory rodents increases their life spans. The life extension varies for each species, but on average there was a 30–40% increase in life span in both mice and rats. In late adulthood, acute CR partially or completely reverses age-related alterations of liver, brain and heart proteins, and mice placed on CR at 19 months of age show an increases in life span.
Fungi models are very easy to manipulate, and many crucial steps toward the understanding of aging have been made with them. Many studies were undertaken on budding yeast and fission yeast to analyze the cellular mechanisms behind increased longevity due to calorie restriction. First, calorie restriction is often called dietary restriction because the same effects on life span can be achieved by only changing the nutrient quality without changing the number of calories. Data from Guarente and others showed that genetic manipulations in nutrient-signaling pathways could mimic the effects of dietary restriction. In some cases, dietary restriction requires mitochondrial respiration to increase longevity (chronological aging), and in some other cases not (replicative aging). Nutrient sensing in yeast controls stress defense, mitochondrial functions, Sir2, and others. These functions are all known to regulate aging. Genes involved in these mechanisms are TOR, PKA, SCH9, MSN2/4, RIM15, and SIR2. Importantly, yeast responses to CR can be modulated by genetic background. Therefore, while some strains respond to calorie restriction with increased lifespan, in others calorie restriction shortens it 
Calorie restriction preserves muscle tissue in nonhuman primates and rodents. Mechanisms include reduced muscle cell apoptosis and inflammation; protection against or adaptation to age-related mitochondrial abnormalities; and preserved muscle stem cell function. Muscle tissue grows when stimulated, so it has been suggested that the calorie-restricted test animals exercised more than their companions on higher calories, perhaps because animals enter a foraging state during calorie restriction. However, studies show that overall activity levels are no higher in calorie restriction than ad libitum animals in youth. Laboratory rodents placed on a calorie restriction diet tend to exhibit increased activity levels (particularly when provided with exercise equipment) at feeding time. Monkeys undergoing calorie restriction also appear more restless immediately before and after meals.
Observations in some accounts of animals undergoing calorie restriction have noted an increase in stereotyped behaviors. For example, monkeys on calorie restriction have demonstrated an increase in licking, sucking, and rocking behavior. A calorie restriction regimen may also lead to increased aggressive behavior in animals.
Preliminary research indicates that sirtuins are activated by fasting and serve as "energy sensors" during metabolism. Sirtuins, specifically Sir2 (found in yeast) have been implicated in the aging of yeast, and are a class of highly conserved, NAD+-dependent histone deacetylase enzymes. Sir2 homologs have been identified in a wide range of organisms from bacteria to humans.
Some research has pointed toward hormesis as an explanation for the benefits of caloric restriction, representing beneficial actions linked to a low-intensity biological stressor such as reduced calorie intake. As a potential role for caloric restriction, the diet imposes a low-intensity biological stress on the organism, eliciting a defensive response that may help protect it against the disorders of aging. In other words, caloric restriction places the organism in a defensive state so that it can survive adversity.
- Vitousek et al. write in 2004, "The relevance of the classic Minnesota study of human CR (Keys et al., 1950) is specifically disavowed (e.g. Heilbronn & Ravussin, 2003; Walford, 2000; Weindruch & Walford, 1988), on the grounds that substandard nutrition must have been responsible for the depression, irritability, social withdrawal, asexuality, fatigue and food preoccupation that subjects experienced."
- Omodei, D; Fontana, L (June 6, 2011). "Very Low Calorie Diet Food Plan". FEBS Lett. 1667 (4): 1. doi:10.1016/j.febslet.2011.03.015. PMC 3439843. PMID 21402069. Archived from the original on June 27, 2019. Retrieved 1 May 2019 – via Jasim Uddin Ahmad.
- Anderson, R. M.; Shanmuganayagam, D.; Weindruch, R. (2009). "Caloric Restriction and Aging: Studies in Mice and Monkeys". Toxicologic Pathology. 37 (1): 47–51. doi:10.1177/0192623308329476. PMC 3734859. PMID 19075044.
- "Can We Prevent Aging?". National Institute on Aging, US National Institutes of Health, Bethesda, MD. 29 July 2016. Archived from the original on 26 September 2016.
- Spindler, Stephen R. (2010). "Biological Effects of Calorie Restriction: Implications for Modification of Human Aging". The Future of Aging. pp. 367–438. doi:10.1007/978-90-481-3999-6_12. ISBN 978-90-481-3998-9.
- Keys A, Brozek J, Henschels A & Mickelsen O & Taylor H. The Biology of Human Starvation, 1950. University of Minnesota Press, Minneapolis
- Keys A 1950, p. 114.
- Keys A 1950, pp. 1213–1214.
- Kalm, Leah M.; Semba, Richard D. (June 1, 2005). "They Starved So That Others Be Better Fed: Remembering Ancel Keys and the Minnesota Experiment". J. Nutr. 135 (6): 1347–1352. doi:10.1093/jn/135.6.1347. PMID 15930436.
- Morley, John E; Chahla, Elie; Alkaade, Saad (2010). "Antiaging, longevity and calorie restriction". Current Opinion in Clinical Nutrition and Metabolic Care. 13 (1): 40–5. doi:10.1097/MCO.0b013e3283331384. PMID 19851100.
- Gower BA, Casazza K (October–December 2013). "Divergent Effects of Obesity on Bone Health". Journal of Clinical Densitometry. 16 (4): 450–454. doi:10.1016/j.jocd.2013.08.010. PMC 5321047. PMID 24063845.
- Bonewald LF, Kiel DP, Clemens TL, Esser K, Orwoll ES, O'Keefe RJ, Fielding RA (September 2013). "Forum on bone and skeletal muscle interactions: Summary of the proceedings of an ASBMR workshop". Journal of Bone and Mineral Research. 28 (9): 1857–1865. doi:10.1002/jbmr.1980. PMC 3749267. PMID 23671010.
- Fontana, L.; Klein, S. (2007). "Aging, Adiposity, and Calorie Restriction". JAMA. 297 (9): 986–94. doi:10.1001/jama.297.9.986. PMID 17341713.
- Hu, Frank (2008). "Interpreting Epidemiologic Evidence and Causal Inference in Obesity Research". In Frank B. Hu (eds.). Obesity Epidemiology. New York, NY: Oxford University Press. pp. 38–52. ISBN 978-0-19-531291-1. Retrieved 2011-02-20.CS1 maint: Uses editors parameter (link)
- Flegal, K. M.; Graubard, B. I.; Williamson, D. F.; Gail, M. H. (2007). "Cause-Specific Excess Deaths Associated With Underweight, Overweight, and Obesity". JAMA. 298 (17): 2028–37. doi:10.1001/jama.298.17.2028. PMID 17986696.
- Holzman, Donald (2005-05-27). "Panel Suggests Methodology Flawed of Recent CDC Obesity Study". Medscape Medical News. Retrieved 2011-02-21.
- "Researchers weigh risks due to overweight". CA: A Cancer Journal for Clinicians. 55 (5): 268–9. 2005. doi:10.3322/canjclin.55.5.268.
- St. Jeor, S. T.; Howard, B. V.; Prewitt, T. E.; Bovee, V.; Bazzarre, T.; Eckel, R. H.; Nutrition Committee Of The Council On Nutrition (2001). "Dietary Protein and Weight Reduction: A Statement for Healthcare Professionals From the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association". Circulation. 104 (15): 1869–74. doi:10.1161/hc4001.096152. PMID 11591629.
- De Souza, RJ; Swain, JF; Appel, LJ; Sacks, FM (2008). "Alternatives for macronutrient intake and chronic disease: a comparison of the OmniHeart diets with popular diets and with dietary recommendations". The American Journal of Clinical Nutrition. 88 (1): 1–11. doi:10.1093/ajcn/88.1.1. PMC 2674146. PMID 18614716.
- Ma, Y; Pagoto, S; Griffith, J; Merriam, P; Ockene, I; Hafner, A; Olendzki, B (2007). "A Dietary Quality Comparison of Popular Weight-Loss Plans". Journal of the American Dietetic Association. 107 (10): 1786–91. doi:10.1016/j.jada.2007.07.013. PMC 2040023. PMID 17904938.
- Binge-Eating Disorder: Clinical Foundations and Treatment (1 ed.). The Guilford Press. 2007. p. 15. ISBN 978-1-59385-594-9.
It can be concluded that caloric restriction does not appear to be associated with the development of binge eating in individuals who have never reported problems with binge eating.
- "Risks". Archived from the original on 2010-09-19. Retrieved 2010-07-28.
- Marzetti, E.; Wohlgemuth, S. E.; Anton, S. D.; Bernabei, R; Carter, C. S.; Leeuwenburgh, C (2012-10-19). "Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives". Clin. Geriatr. Med. 25 (4): 715–32, ix. doi:10.1016/j.cger.2009.07.002. PMC 2786899. PMID 19944269.
- Conti, B; Sanchez-Alavez, M; Winsky-Sommerer, R; Morale, MC; Lucero, J; Brownell, S; Fabre, V; Huitron-Resendiz, S; Henriksen, S; Zorrilla, EP; de Lecea, L; Bartfai, T (3 November 2006). "Transgenic mice with a reduced core body temperature have an increased life span". Science. 314 (5800): 825–8. Bibcode:2006Sci...314..825C. doi:10.1126/science.1132191. PMID 17082459.
- Nikolai, Sibylle; Pallauf, Kathrin; Huebbe, Patricia; Rimbach, Gerald (22 September 2015). "Energy restriction and potential energy restriction mimetics". Nutrition Research Reviews. 28 (2): 100–120. doi:10.1017/S0954422415000062. PMID 26391585. Retrieved 8 November 2015.
- Cangemi, Roberto; Friedmann, Alberto J.; Holloszy, John O.; Fontana, Luigi (2010). "Long-term effects of calorie restriction on serum sex-hormone concentrations in men". Aging Cell. 9 (2): 236–42. doi:10.1111/j.1474-9726.2010.00553.x. PMC 3569090. PMID 20096034.
- Bergamini, E; Cavallini, G; Donati, A; Gori, Z (2003). "The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically". Biomedicine & Pharmacotherapy. 57 (5–6): 203–8. doi:10.1016/S0753-3322(03)00048-9.
- Cuervo, Ana Maria; Bergamini, Ettore; Brunk, Ulf T; Dröge, Wulf; Ffrench, Martine; Terman, Alexei (2005). "Autophagy and Aging: the Importance of Maintaining "Clean" Cells". Autophagy. 1 (3): 131–40. doi:10.4161/auto.1.3.2017. PMID 16874025.
- Mattson MP (2005). "Energy intake, meal frequency, and health: a neurobiological perspective". Annu. Rev. Nutr. (Review). 25: 237–60. doi:10.1146/annurev.nutr.25.050304.092526. PMID 16011467.
- Mattison, Julie A; Colman, Ricki J; Beasley, T Mark; Allison, David B; Kemnitz, Joseph W; Roth, George S; Ingram, Donald K; Weindruch, Richard; De Cabo, Rafael; Anderson, Rozalyn M (2017). "Caloric restriction improves health and survival of rhesus monkeys". Nature Communications. 8: 14063. Bibcode:2017NatCo...814063M. doi:10.1038/ncomms14063. PMC 5247583. PMID 28094793.
- Urbanski, H F.; Downs, J L; Garyfallou, V T; Mattison, J A; Lane, M A; Roth, G S; Ingram, D K (2004). "Effect of Caloric Restriction on the 24-Hour Plasma DHEAS and Cortisol Profiles of Young and Old Male Rhesus Macaques". Annals of the New York Academy of Sciences. 1019: 443–7. doi:10.1196/annals.1297.081. PMID 15247063.
- Schäfer, Daniel (Mar–Apr 2005). "Aging, Longevity, and Diet: Historical Remarks on Calorie Intake Reduction". Gerontology. 51 (2): 126–30. doi:10.1159/000082198. PMID 15711080.
- Cornaro, Luigi (1550). Discourses and Letters on the Sober and Temperate Life. Internet Archive. Retrieved November 13, 2017.
- Everitt, Heilbronn & Le Couteur 2010, p. 15.
- Benedict, Francis G.; Miles, Walter R.; Roth, Paul; Smith, H. Monmouth (1919). Human Vitality and Efficiency Under Prolonged Restricted Diet. Carnegie Institution of Washington. Retrieved November 13, 2017.
- Keys et al. 1950, pp. 35–36.
- Everitt, Heilbronn & Le Couteur 2010, p. 17.
- Vitousek, Kelly M.; Manke1, Frederic P.; Gray, Jennifer A.; Vitousek, Maren N. (2004). "Caloric Restriction for Longevity: II—The Systematic Neglect of Behavioural and Psychological Outcomes in Animal Research". Eur. Eat. Disorders Rev. 12 (6): 338–360. doi:10.1002/erv.604.
- Everitt, Heilbronn & Le Couteur 2010, p. 18.
- Vallejo, EA (January 11, 1957). "Hunger diet on alternate days in the nutrition of the aged". Prensa Med Argent (in Spanish). 44 (2): 119–20. PMID 13453175.
- Redman, Leanne M.; Ravussin, Eric (December 2010). "Caloric Restriction in Humans: Impact on Physiological, Psychological, and Behavioral Outcomes". Antioxidants & Redox Signaling. 14 (2): 275–287. doi:10.1089/ars.2010.3253. PMC 3014770. PMID 20518700.
- Phelan, J; Rose, M (2005). "Why dietary restriction substantially increases longevity in animal models but won't in humans". Ageing Research Reviews. 4 (3): 339–50. doi:10.1016/j.arr.2005.06.001. PMID 16046282.
- Everitt, A. V; Le Couteur, D. G (2007). "Life extension by calorie restriction in humans". Annals of the New York Academy of Sciences. 1114 (1): 428–33. Bibcode:2007NYASA1114..428E. doi:10.1196/annals.1396.005. PMID 17717102.
- "Calorie restriction lets monkeys live long and prosper". ScienceDirect. 17 January 2017. Retrieved 15 February 2017.
- Spindler, S (2005). "Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction". Mechanisms of Ageing and Development. 126 (9): 960–6. doi:10.1016/j.mad.2005.03.016. PMID 15927235.
- Kaeberlein, Matt; Burtner, Christopher R.; Kennedy, Brian K. (2007). "Recent Developments in Yeast Aging". PLoS Genetics. 3 (5): e84. doi:10.1371/journal.pgen.0030084. PMC 1877880. PMID 17530929.
- Dilova, I.; Easlon, E.; Lin, S. -J. (2007). "Calorie restriction and the nutrient sensing signaling pathways". Cellular and Molecular Life Sciences. 64 (6): 752–67. doi:10.1007/s00018-007-6381-y. PMID 17260088.
- Chen, D; Guarente, L (2007). "SIR2: a potential target for calorie restriction mimetics". Trends in Molecular Medicine. 13 (2): 64–71. doi:10.1016/j.molmed.2006.12.004. PMID 17207661.
- Piper, Peter W. (2006). "Long-lived yeast as a model for ageing research". Yeast. 23 (3): 215–26. doi:10.1002/yea.1354. PMID 16498698.
- Longo, V (2009). "Linking sirtuins, IGF-I signaling, and starvation". Experimental Gerontology. 44 (1–2): 70–4. doi:10.1016/j.exger.2008.06.005. PMID 18638538.
- Schleit J.; Wasko B.M.; Kaeberlein M. (2012). "Yeast as a model to understand the interaction between genotype and the response to calorie restriction". FEBS Lett. 586 (18): 2868–2873. doi:10.1016/j.febslet.2012.07.038. PMC 4016815. PMID 22828279.
- McKiernan, SH; Colman, RJ; Aiken, E; Evans, TD; Beasley, TM; Aiken, JM; Weindruch, R; Anderson, RM (Mar 2012). "Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys". Exp Gerontol. 47 (3): 229–36. doi:10.1016/j.exger.2011.12.009. PMC 3321729. PMID 22226624.
- Colman, RJ; Beasley, TM; Allison, DB; Weindruch, R (2008). "Attenuation of Sarcopenia by Dietary Restriction in Rhesus Monkeys". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 63 (6): 556–9. doi:10.1093/gerona/63.6.556. PMC 2812805. PMID 18559628.
- Dirks Naylor, AJ; Leeuwenburgh, C (Jan 2008). "Sarcopenia: the role of apoptosis and modulation by caloric restriction". Exerc Sport Sci Rev. 36 (1): 19–24. doi:10.1097/jes.0b013e31815ddd9d. PMID 18156949.
- Bua, E; McKiernan, SH; Aiken, JM (Mar 2004). "Calorie restriction limits the generation but not the progression of mitochondrial abnormalities in aging skeletal muscle". FASEB J. 18 (3): 582–4. doi:10.1096/fj.03-0668fje. PMID 14734641.
- Cerletti, M; Jang, YC; Finley3=LW; Haigis 4=MC; Wagers 5=AJ (May 4, 2012). "Short-term calorie restriction enhances skeletal muscle stem cell function". Cell Stem Cell. 10 (5): 515–9. doi:10.1016/j.stem.2012.04.002. PMC 3561899. PMID 22560075.
- Faulks, SC; Turner, N; Else, PL; Hulbert, AJ (Aug 2006). "Calorie restriction in mice: effects on body composition, daily activity, metabolic rate, mitochondrial reactive oxygen species production, and membrane fatty acid composition". J Gerontol A Biol Sci Med Sci. 61 (8): 781–94. doi:10.1093/gerona/61.8.781. PMID 16912094.
- Vitousek K. M.; Manke F. P.; Gray J. A.; Vitousek M. N. (2004). "Caloric Restriction for Longevity: II--The Systematic Neglect of Behavioural and Psychological Outcomes in Animal Research". European Eating Disorders Review. 12 (6): 338–360. doi:10.1002/erv.604.
- Weed J. L.; Lane M. A.; Roth G. S.; Speer D. L.; Ingram D. K. (1997). "Activity measures in rhesus monkeys on long-term calorie restriction". Physiology & Behavior. 62: 97–103. doi:10.1016/s0031-9384(97)00147-9.
- Chang, H. C; Guarente, L (2013). "SIRT1 and other sirtuins in Metabolism". Trends in Endocrinology and Metabolism. 25 (3): 138–145. doi:10.1016/j.tem.2013.12.001. hdl:1721.1/104067. PMC 3943707. PMID 24388149.
- Guarente, L. (2007). "Sirtuins in aging and disease". Cold Spring Harbor Symposia on Quantitative Biology. 72: 483–488. doi:10.1101/sqb.2007.72.024. ISSN 0091-7451. PMID 18419308.
- Lin, Su-Ju; Ford, Ethan; Haigis, Marcia; Liszt, Greg; Guarente, Leonard (2004-01-01). "Calorie restriction extends yeast life span by lowering the level of NADH". Genes & Development. 18 (1): 12–16. doi:10.1101/gad.1164804. ISSN 0890-9369. PMC 314267. PMID 14724176.
- Kaeberlein M.; McVey M.; Guarente L. (1999). "The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. '". Genes & Development. 13 (19): 2570–2580. doi:10.1101/gad.13.19.2570. PMC 317077. PMID 10521401.
- Martins, I; Galluzzi, L; Kroemer, G (2011). "Hormesis, cell death and aging". Aging. 3 (9): 821–8. doi:10.18632/aging.100380. PMC 3227447. PMID 21931183.
- Everitt, Arthur V.; Heilbronn, Leonie K.; Le Couteur, David G. (2010). "Food Intake, Life Style, Aging and Human Longevity". In Everitt, Arthur V; Rattan, Suresh IS; Le Couteur, David G; de Cabo, Rafael (eds.). Calorie Restriction, Aging and Longevity. New York: Springer. ISBN 978-90-481-8555-9.
- Keys, Ancel; Brozek, Josef; Henschel, Austin; Mickelsen, Olaf; Taylor, Henry Longstreet (1950). The Biology of Human Starvation. I. University of Minnesota Press. ISBN 9780816672349.