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Caloric restriction and its mimetics
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  • Journal title : BMB Reports
  • Volume 46, Issue 4,  2013, pp.181-187
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2013.46.4.033
 Title & Authors
Caloric restriction and its mimetics
Lee, Shin-Hae; Min, Kyung-Jin;
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Caloric restriction is the most reliable intervention to prevent age-related disorders and extend lifespan. The reduction of calories by 10-30% compared to an ad libitum diet is known to extend the longevity of various species from yeast to rodents. The underlying mechanisms by which the benefits of caloric restriction occur have not yet been clearly defined. However, many studies are being conducted in an attempt to elucidate these mechanisms, and there are indications that the benefits of caloric restriction are related to alteration of the metabolic rate and the accumulation of reactive oxygen species. During molecular signaling, insulin/insulin-like growth factor signaling, target of rapamycin pathway, adenosine monophosphate activated protein kinase signaling, and Sirtuin are focused as underlying pathways that mediate the benefits of caloric restriction. Here, we will review the current status of caloric restriction.
Caloric restriction;CR mimetics;Lifespan extension;Longevity;
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Fontana, L., Partridge, L. and Longo, V. D. (2010) Extending healthy life span--from yeast to humans. Science 328, 321-326. crossref(new window)

Masoro, E. J. (2005) Overview of caloric restriction and ageing. Mech. Ageing Dev. 126, 913-922. crossref(new window)

Speakman, J. R. and Mitchell, S. E. (2011) Caloric restriction. Mol. Aspects Med. 32, 159-221. crossref(new window)

Fontana, L., Weiss, E. P., Villareal, D. T., Klein, S. and Holloszy, J. O. (2008) Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7, 681-687. crossref(new window)

Orentreich, N., Matias, J. R., DeFelice, A. and Zimmerman, J. A. (1993) Low methionine ingestion by rats extends life span. J. Nutr. 123, 269-274.

Ooka, H., Segall, P. E. and Timiras, P. S. (1988) Histology and survival in age-delayed low-tryptophan-fed rats. Mech. Ageing Dev. 43, 79-98. crossref(new window)

Osborne, T. B., Mendel, L. B. and Ferry, E. L. (1917) The effect of retardation of growth upon the breeding period and duration of life of rats. Science 45, 294-295. crossref(new window)

Robertson, T. B. and Ray, L. A. (1920) Experimental studies on growth: XV. On the growth of relatively long lived compared with that of relatively short lived animals. J. Biol. Chem. 42, 71-107.

McCay, C. M., Crowell, M. F. and Maynard, L. A. (1989) The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5, 155-171.

Weindruch, R., Walford, R. L., Fligiel, S. and Guthrie, D. (1986) The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116, 641-654.

Fabrizio, P. and Longo, V. D. (2003) The chronological life span of Saccharomyces cerevisiae. Aging Cell 2, 73-81.

Lin, S. J., Defossez, P. A. and Guarente, L. (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289, 2126-2128. crossref(new window)

Wei, M., Fabrizio, P., Hu, J., Ge, H., Cheng, C., Li, L. and Longo, V. D. (2008) Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet. 4, e13. crossref(new window)

Houthoofd, K., Braeckman, B. P., Lenaerts, I., Brys, K., De Vreese, A., Van Eygen, S. and Vanfleteren, J. R. (2002) Axenic growth up-regulates mass-specific metabolic rate, stress resistance, and extends life span in Caenorhabditis elegans. Exp. Gerontol. 37, 1371-1378. crossref(new window)

Mair, W., Piper, M. D. and Partridge, L. (2005) Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol. 3, e223. crossref(new window)

Simpson, S. J. and Raubenheimer, D. (2009) Macronutrient balance and lifespan. Aging (Albany NY) 1, 875-880.

McCay, C. M., Crowell, M. F. and Maynard, L. A. (1935) The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10, 63-79.

Varady, K. A. and Hellerstein, M. K. (2007) Alternate-day fasting and chronic disease prevention: a review of human and animal trials. Am. J. Clin. Nutr. 86, 7-13.

Singh, R., Lakhanpal, D., Kumar, S., Sharma, S., Kataria, H., Kaur, M. and Kaur, G. (2012) Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age (Dordr) 34, 917-933. crossref(new window)

Bodkin, N. L., Alexander, T. M., Ortmeyer, H. K., Johnson, E. and Hansen, B. C. (2003) Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction. J. Gerontol. A. Biol. Sci. Med. Sci. 58, 212-219. crossref(new window)

Bodkin, N. L., Ortmeyer, H. K. and Hansen, B. C. (1995) Long-term dietary restriction in older-aged rhesus monkeys: effects on insulin resistance. J. Gerontol. A. Biol. Sci. Med. Sci. 50, B142-147.

Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W. and Weindruch, R. (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201-204. crossref(new window)

Mattison, J. A., Roth, G. S., Beasley, T. M., Tilmont, E. M., Handy, A. M., Herbert, R. L., Longo, D. L., Allison, D. B., Young, J. E., Bryant, M., Barnard, D., Ward, W. F., Qi, W., Ingram, D. K. and de Cabo, R. (2012) Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318-321. crossref(new window)

Hallak, M. H. and Nomani, M. Z. (1988) Body weight loss and changes in blood lipid levels in normal men on hypocaloric diets during Ramadan fasting. Am. J. Clin. Nutr. 48, 1197-1210.

Maislos, M., Khamaysi, N., Assali, A., Abou-Rabiah, Y., Zvili, I. and Shany, S. (1993) Marked increase in plasma high-density-lipoprotein cholesterol after prolonged fasting during Ramadan. Am. J. Clin. Nutr. 57, 640-642.

Rickman, A. D., Williamson, D. A., Martin, C. K., Gilhooly, C. H., Stein, R. I., Bales, C. W., Roberts, S. and Das, S. K. (2011) The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. Contemp. Clin. Trials. 32, 874-881. crossref(new window)

Meydani, M., Das, S., Band, M., Epstein, S. and Roberts, S. (2011) The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the CALERIE Trial of Human Caloric Restriction. J. Nutr. Health. Aging 15, 456-460. crossref(new window)

Martin, C. K., Das, S. K., Lindblad, L., Racette, S. B., McCrory, M. A., Weiss, E. P., Delany, J. P. and Kraus, W. E. (2011) Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials. J. Appl. Physiol. 110, 956-963. crossref(new window)

Villareal, D. T., Fontana, L., Weiss, E. P., Racette, S. B., Steger-May, K., Schechtman, K. B., Klein, S. and Holloszy, J. O. (2006) Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch. Intern. Med. 166, 2502-2510. crossref(new window)

Weiss, E. P., Racette, S. B., Villareal, D. T., Fontana, L., Steger-May, K., Schechtman, K. B., Klein, S., Ehsani, A. A. and Holloszy, J. O. (2007) Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. J. Appl. Physiol. 102, 634-640.

Pearl, R., Winsor, A. A. and Miner, J. R. (1928) The growth of seedlings of the canteloup, cucumis melo, in the absence of exogenous food and light. Proc. Natl. Acad. Sci. U.S.A. 14, 1-4. crossref(new window)

Hayflick, L. (2004) The not-so-close relationship between biological aging and age-associated pathologies in humans. J. Gerontol. A. Biol. Sci. Med. Sci. 59, B547-550. crossref(new window)

Merry, B. J. (2002) Molecular mechanisms linking calorie restriction and longevity. Int. J. Biochem. Cell Biol. 34, 1340-1354. crossref(new window)

Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S. R., Alderson, N. L., Baynes, J. W., Epstein, C. J., Huang, T. T., Nelson, J., Strong, R. and Richardson, A. (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol. Genomics 16, 29-37.

Miwa, S., Riyahi, K., Partridge, L. and Brand, M. D. (2004) Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila. Ann. N. Y. Acad. Sci. 1019, 388-391. crossref(new window)

Tabarean, I., Morrison, B., Marcondes, M. C., Bartfai, T. and Conti, B. (2010) Hypothalamic and dietary control of temperature-mediated longevity. Ageing Res. Rev. 9, 41-50. crossref(new window)

Salih, D. A. and Brunet, A. (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr. Opin. Cell Biol. 20, 126-136. crossref(new window)

Kenyon, C., Chang, J., Gensch, E., Rudner, A. and Tabtiang, R. (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366, 461-464. crossref(new window)

Min, K. J., Yamamoto, R., Buch, S., Pankratz, M. and Tatar, M. (2008) Drosophila lifespan control by dietary restriction independent of insulin-like signaling. Aging Cell 7, 199-206. crossref(new window)

McKee Alderman, J., DePetrillo, M. A., Gluesenkamp, A. M., Hartley, A. C., Verhoff, S. V., Zavodni, K. L. and Combs, T. P. (2010) Calorie restriction and dwarf mice in gerontological research. Gerontology 56, 404-409. crossref(new window)

Jia, K., Chen, D. and Riddle, D. L. (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897-3906. crossref(new window)

Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V. and Benzer, S. (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885-890. crossref(new window)

Dogan, S., Johannsen, A. C., Grande, J. P. and Cleary, M. P. (2011) Effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mTOR) and IGF-I signaling pathways in mammary fat pad tissues and mammary tumors. Nutr. Cancer 63, 389-401. crossref(new window)

Sharma, N., Castorena, C. M. and Cartee, G. D. (2012) Tissue-specific responses of IGF-1/insulin and mTOR signaling in calorie restricted rats. PLoS One 7, e38835. crossref(new window)

Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M. and Ristow, M. (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6, 280-293. crossref(new window)

Greer, E. L., Dowlatshahi, D., Banko, M. R., Villen, J., Hoang, K., Blanchard, D., Gygi, S. P. and Brunet, A. (2007) An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr. Biol. 17, 1646-1656. crossref(new window)

Funakoshi, M., Tsuda, M., Muramatsu, K., Hatsuda, H., Morishita, S. and Aigaki, T. (2011) A gain-of-function screen identifies wdb and lkb1 as lifespan-extending genes in Drosophila. Biochem. Biophys. Res. Commun. 405, 667-672. crossref(new window)

Stenesen, D., Suh, J. M., Seo, J., Yu, K., Lee, K. S., Kim, J. S., Min, K. J. and Graff, J. M. (2013) Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies. Cell Metab. 17, 101-112. crossref(new window)

Canto, C. and Auwerx, J. (2011) Calorie restriction: is AMPK a key sensor and effector? Physiology (Bethesda) 26, 214-224. crossref(new window)

Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., Moncada, S. and Carruba, M. O. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310, 314-317. crossref(new window)

Rogina, B. and Helfand, S. L. (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. U.S.A. 101, 15998-16003. crossref(new window)

Tissenbaum, H. A. and Guarente, L. (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227-230. crossref(new window)

Bordone, L., Cohen, D., Robinson, A., Motta, M. C., van Veen, E., Czopik, A., Steele, A. D., Crowe, H., Marmor, S., Luo, J., Gu, W. and Guarente, L. (2007) SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 6, 759-767. crossref(new window)

Boily, G., Seifert, E. L., Bevilacqua, L., He, X. H., Sabourin, G., Estey, C., Moffat, C., Crawford, S., Saliba, S., Jardine, K., Xuan, J., Evans, M., Harper, M. E. and McBurney, M. W. (2008) SirT1 regulates energy metabolism and response to caloric restriction in mice. PLoS One 3, e1759. crossref(new window)

Kaeberlein, M., Powers, R. W. 3rd, Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S. and Kennedy, B. K. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193-1196. crossref(new window)

Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L. L., Scherer, B. and Sinclair, D. A. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191-196. crossref(new window)

Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M. and Sinclair, D. (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430, 686-689. crossref(new window)

Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., Pistell, P. J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., Lakatta, E. G., Le Couteur, D., Shaw, R. J., Navas, P., Puigserver, P., Ingram, D. K., de Cabo, R. and Sinclair, D. A. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337-342. crossref(new window)

Pearson, K. J., Baur, J. A., Lewis, K. N., Peshkin, L., Price, N. L., Labinskyy, N., Swindell, W. R., Kamara, D., Minor, R. K., Perez, E., Jamieson, H. A., Zhang, Y., Dunn, S. R., Sharma, K., Pleshko, N., Woollett, L. A., Csiszar, A., Ikeno, Y., Le Couteur, D., Elliott, P. J., Becker, K. G., Navas, P., Ingram, D. K., Wolf, N. S., Ungvari, Z., Sinclair, D. A. and de Cabo, R. (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 8, 157-168. crossref(new window)

Powers, R. W. 3rd, Kaeberlein, M., Caldwell, S. D., Kennedy, B. K. and Fields, S. (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 20, 174-184. crossref(new window)

Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., Pahor, M., Javors, M. A., Fernandez, E. and Miller, R. A. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392-395.

Blattler, S. M., Cunningham, J. T., Verdeguer, F., Chim, H., Haas, W., Liu, H., Romanino, K., Ruegg, M. A., Gygi, S. P., Shi, Y. and Puigserver, P. (2012) Yin Yang 1 deficiency in skeletal muscle protects against rapamycin-induced diabetic-like symptoms through activation of insulin/IGF signaling. Cell Metab. 15, 505-517. crossref(new window)

Dhahbi, J. M., Mote, P. L., Fahy, G. M. and Spindler, S. R. (2005) Identification of potential caloric restriction mimetics by microarray profiling. Physiol. Genomics. 23, 343-350. crossref(new window)

Onken, B. and Driscoll, M. (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS One 5, e8758. crossref(new window)

Slack, C., Foley, A. and Partridge, L. (2012) Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS One 7, e47699. crossref(new window)

Smith, D. L. Jr., Nagy, T. R. and Allison, D. B. (2010) Calorie restriction: what recent results suggest for the future of ageing research. Eur. J. Clin. Invest. 40, 440-450. crossref(new window)