Protein Quantity and Source, Fasting-Mimicking Diets, and Longevity

Sebastian Brandhorst, Valter D Longo, Sebastian Brandhorst, Valter D Longo

Abstract

Dietary modifications, including caloric restriction, dietary restriction, various intervals of fasting, and even limiting the time when food is consumed can have a pronounced impact on longevity. In addition, dietary modifications are powerful interventions to delay, prevent, or treat many aging-related diseases such as cancer and diabetes. Restricting amino acid and protein intake generally decreases aging-related comorbidities and thereby increases health and longevity. However, chronic dietary interventions are likely not feasible for most people due to low adherence to dietary protocols or resistance to drastic changes to lifestyle, and might even cause detrimental effects, possibly by negatively affecting the immune system and wound healing. The periodic use of low-protein, low-calorie fasting-mimicking diets (FMDs) has the potential to promote health benefits, while minimizing the burden of chronic restriction. Protein restriction and FMDs together have the potential to play an important complementary role in medicine by promoting disease prevention and treatment, and by delaying the aging process at least in part by stimulating stem cell-based regeneration in periods of normal food intake after periodic FMD cycles. The aim of this narrative review is to summarize research on the impact of protein restriction on health and longevity in model organisms and to discuss the implementation of an FMD in mice and in human clinical trials and its effects on biomarkers of healthy aging. Taking into account the importance of sex on aging and diet, we include this information in all discussed studies. Whereas for some model organisms of aging, such as rodents, many studies are available, results are more limited for primates and/or humans.

Keywords: fasting-mimicking diet; healthspan; longevity; protein intake; protein source.

Copyright © The Author(s) 2019.

Figures

FIGURE 1
FIGURE 1
Effects of low-protein-based and plant-protein-based diets, fasting, and fasting-mimicking diets.

References

    1. Fontana L, Partridge L, Longo VD. Extending healthy life span–from yeast to humans. Science. 2010;328(5976):321–6.
    1. Mirzaei H, Suarez JA, Longo VD. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol Metab. 2014;25(11):558–66.
    1. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366(6454):461–4.
    1. Johnson TE. Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science. 1990;249(4971):908–12.
    1. Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD. Regulation of longevity and stress resistance by Sch9 in yeast. Science. 2001;292(5515):288–90.
    1. Longo VD. Mutations in signal transduction proteins increase stress resistance and longevity in yeast, nematodes, fruit flies, and mammalian neuronal cells. Neurobiol Aging. 1999;20(5):479–86.
    1. Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003;299(5611):1346–51.
    1. Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature. 2000;408(6809):255–62.
    1. Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell. 2005;120(4):449–60.
    1. Brown-Borg HM. Hormonal control of aging in rodents: the somatotropic axis. Mol Cell Endocrinol. 2009;299(1):64–71.
    1. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384(6604):33.
    1. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, Hwang D, Martin-Montalvo A, Saavedra J, Ingles S et al. .. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3(70):70ra13.
    1. Wei M, Fabrizio P, Hu J, Ge H, Cheng C, Li L, Longo VD. Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet. 2008;4(1):e13.
    1. Mirisola MG, Taormina G, Fabrizio P, Wei M, Hu J, Longo VD. Serine- and threonine/valine-dependent activation of PDK and Tor orthologs converge on Sch9 to promote aging. PLoS Genet. 2014;10(2):e1004113.
    1. Lapierre LR, Hansen M. Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab. 2012;23(12):637–44.
    1. Depuydt G, Xie F, Petyuk VA, Shanmugam N, Smolders A, Dhondt I, Brewer HM, Camp DG 2nd, Smith RD, Braeckman BP. Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans. Mol Cell Proteomics. 2013;12(12):3624–39.
    1. Tatar M, Post S, Yu K. Nutrient control of Drosophila longevity. Trends Endocrinol Metab. 2014;25(10):509–17.
    1. Greer EL, Brunet A. Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell. 2009;8(2):113–27.
    1. Rousakis A, Vlassis A, Vlanti A, Patera S, Thireos G, Syntichaki P. The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans. Aging Cell. 2013;12(5):742–51.
    1. Minor RK, Allard JS, Younts CM, Ward TM, de Cabo R. Dietary interventions to extend life span and health span based on calorie restriction. J Gerontol A Biol Sci Med Sci. 2010;65(7):695–703.
    1. Mair W, Piper MD, Partridge L. Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol. 2005;3(7):e223.
    1. Bruce KD, Hoxha S, Carvalho GB, Yamada R, Wang HD, Karayan P, He S, Brummel T, Kapahi P, Ja WW. High carbohydrate-low protein consumption maximizes Drosophila lifespan. Exp Gerontol. 2013;48(10):1129–35.
    1. Longo VD, Finch CE. Evolutionary medicine: from dwarf model systems to healthy centenarians?. Science. 2003;299(5611):1342–6.
    1. Mitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, Chu T, Forrer F, Muller C, de Jong M et al. .. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell. 2009;9(1):40–53.
    1. Peng W, Robertson L, Gallinetti J, Mejia P, Vose S, Charlip A, Chu T, Mitchell JR. Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. Sci Transl Med. 2012;4(118):118ra11.
    1. Ayala V, Naudi A, Sanz A, Caro P, Portero-Otin M, Barja G, Pamplona R. Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. J Gerontol A Biol Sci Med Sci. 2007;62(4):352–60.
    1. Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell. 2005;4(3):119–25.
    1. Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993;123(2):269–74.
    1. Pamplona R, Barja G. Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection. Biochim Biophys Acta. 2006;1757(5-6):496–508.
    1. Xiao F, Huang Z, Li H, Yu J, Wang C, Chen S, Meng Q, Cheng Y, Gao X, Li J et al. .. Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes. 2011;60(3):746–56.
    1. Mirzaei H, Raynes R, Longo VD. The conserved role of protein restriction in aging and disease. Curr Opin Clin Nutr Metab Care. 2016;19(1):74–9.
    1. Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA et al. .. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 2016;16(2):520–30.
    1. Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI et al. .. Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 2018;596(4):623–45.
    1. Parrella E, Maxim T, Maialetti F, Zhang L, Wan J, Wei M, Cohen P, Fontana L, Longo VD. Protein restriction cycles reduce IGF-1 and phosphorylated Tau, and improve behavioral performance in an Alzheimer's disease mouse model. Aging Cell. 2013;12(2):257–68.
    1. Segall P. Long-term tryptophan restriction and aging in the rat. Aktuelle Gerontol. 1977;7(10):535–8.
    1. Spindler SR. Caloric restriction: from soup to nuts. Ageing Res Rev. 2010;9(3):324–53.
    1. Gietzen DW, Hao S, Anthony TG. Mechanisms of food intake repression in indispensable amino acid deficiency. Annu Rev Nutr. 2007;27:63–78.
    1. Robertson LT, Trevino-Villarreal JH, Mejia P, Grondin Y, Harputlugil E, Hine C, Vargas D, Zheng H, Ozaki CK, Kristal BS et al. .. Protein and calorie restriction contribute additively to protection from renal ischemia reperfusion injury partly via leptin reduction in male mice. J Nutr. 2015;145(8):1717–27.
    1. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG et al. .. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418–30.
    1. Solon-Biet SM, Mitchell SJ, Coogan SC, Cogger VC, Gokarn R, McMahon AC, Raubenheimer D, de Cabo R, Simpson SJ, Le Couteur DG. Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice. Cell Rep. 2015;11(10):1529–34.
    1. Solon-Biet SM, Mitchell SJ, de Cabo R, Raubenheimer D, Le Couteur DG, Simpson SJ. Macronutrients and caloric intake in health and longevity. J Endocrinol. 2015;226(1):R17–28.
    1. Lopez-Bermejo A, Buckway CK, Rosenfeld RG. Genetic defects of the growth hormone-insulin-like growth factor axis. Trends Endocrinol Metab. 2000;11(2):39–49.
    1. Fontana L, Kennedy BK, Longo VD, Seals D, Melov S. Medical research: treat ageing. Nature. 2014;511(7510):405–7.
    1. Yang J, Anzo M, Cohen P. Control of aging and longevity by IGF-I signaling. Exp Gerontol. 2005;40(11):867–72.
    1. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 2010;11(6):453–65.
    1. Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun. 2014;5:3557.
    1. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M et al. .. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature. 2012;489(7415):318–21.
    1. Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD. Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;96(6):1281–98.
    1. Santesso N, Akl EA, Bianchi M, Mente A, Mustafa R, Heels-Ansdell D, Schunemann HJ. Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. Eur J Clin Nutr. 2012;66(7):780–8.
    1. Tielemans SM, Altorf-van der Kuil W, Engberink MF, Brink EJ, van Baak MA, Bakker SJ, Geleijnse JM. Intake of total protein, plant protein and animal protein in relation to blood pressure: a meta-analysis of observational and intervention studies. J Hum Hypertens. 2013;27(9):564–71.
    1. Westerterp-Plantenga MS, Nieuwenhuizen A, Tome D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr. 2009;29:21–41.
    1. Clifton P. High-protein and low-glycaemic diets improve dietary compliance and maintenance of weight loss in overweight adults who have lost weight on a low-calorie diet. BMJ Evid Based Med. 2011;16(4):112–3.
    1. Lagiou P, Sandin S, Lof M, Trichopoulos D, Adami HO, Weiderpass E. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. BMJ. 2012;344:e4026.
    1. Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med. 2010;153(5):289–98.
    1. Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J et al. .. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014;19(3):407–17.
    1. Giovannucci E, Pollak M, Liu Y, Platz EA, Majeed N, Rimm EB, Willett WC. Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomarkers Prev. 2003;12(2):84–9.
    1. Smith GD, Gunnell D, Holly J. Cancer and insulin-like growth factor-I. A potential mechanism linking the environment with cancer risk. BMJ. 2000;321(7265):847–8.
    1. Chang SF, Lin PL. Frail phenotype and mortality prediction: a systematic review and meta-analysis of prospective cohort studies. Int J Nurs Stud. 2015;52(8):1362–74.
    1. Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol. 2011;164(4):485–9.
    1. Kinney-Forshee BA, Kinney NE, Steger RW, Bartke A. Could a deficiency in growth hormone signaling be beneficial to the aging brain?. Physiol Behav. 2004;80(5):589–94.
    1. Nashiro K, Guevara-Aguirre J, Braskie MN, Hafzalla GW, Velasco R, Balasubramanian P, Wei M, Thompson PM, Mather M, Nelson MD et al. .. Brain structure and function associated with younger adults in growth hormone receptor-deficient humans. J Neurosci. 2017;37(7):1696–707.
    1. Appel LJ. Dietary patterns and longevity: expanding the blue zones. Circulation. 2008;118(3):214–5.
    1. Willcox BJ, Willcox DC, Todoriki H, Fujiyoshi A, Yano K, He Q, Curb JD, Suzuki M. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007;1114:434–55.
    1. Mishra BN. Secret of eternal youth; teaching from the centenarian hot spots (“blue zones”). Indian J Community Med. 2009;34(4):273–5.
    1. Chrysohoou C, Pitsavos C, Lazaros G, Skoumas J, Tousoulis D, Stefanadis C. Determinants of all-cause mortality and incidence of cardiovascular disease (2009 to 2013) in older adults: The Ikaria study of the blue zones. Angiology. 2016;67(6):541–8.
    1. Davinelli S, Willcox DC, Scapagnini G. Extending healthy ageing: nutrient sensitive pathway and centenarian population. Immun Ageing. 2012;9:9.
    1. Lamming DW, Baar EL, Arriola Apelo SI, Tosti V, Fontana L. Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice. Nutr Healthy Aging. 2017;4(3):239–45.
    1. Carroll KK. Hypercholesterolemia and atherosclerosis: effects of dietary protein. Fed Proc. 1982;41(11):2792–6.
    1. Kritchevsky D, Tepper SA, Czarnecki SK, Klurfeld DM, Story JA. Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 9. Beef protein and textured vegetable protein. Atherosclerosis. 1981;39(2):169–75.
    1. Campbell TC. A plant-based diet and animal protein: questioning dietary fat and considering animal protein as the main cause of heart disease. J Geriatr Cardiol. 2017;14(5):331–7.
    1. Terpstra AH, Woodward CJ, West CE, Van Boven HG. A longitudinal cross-over study of serum cholesterol and lipoproteins in rabbits fed on semi-purified diets containing either casein or soya-bean protein. Br J Nutr. 1982;47(2):213–21.
    1. Terpstra AH, Harkes L, van der Veen FH. The effect of different proportions of casein in semipurified diets on the concentration of serum cholesterol and the lipoprotein composition in rabbits. Lipids. 1981;16(2):114–9.
    1. Kritchevsky D, Tepper SA, Czarnecki SK, Klurfeld DM. Atherogenicity of animal and vegetable protein. Influence of the lysine to arginine ratio. Atherosclerosis. 1982;41(2-3):429–31.
    1. Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A et al. .. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591–608.
    1. Couzin-Frankel J. Nutrition. Diet studies challenge thinking on proteins versus carbs. Science. 2014;343(6175):1068.
    1. Kelemen LE, Kushi LH, Jacobs DR Jr, Cerhan JR. Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. Am J Epidemiol. 2005;161(3):239–49.
    1. Preis SR, Stampfer MJ, Spiegelman D, Willett WC, Rimm EB. Lack of association between dietary protein intake and risk of stroke among middle-aged men. Am J Clin Nutr. 2010;91(1):39–45.
    1. Preis SR, Stampfer MJ, Spiegelman D, Willett WC, Rimm EB. Dietary protein and risk of ischemic heart disease in middle-aged men. Am J Clin Nutr. 2010;92(5):1265–72.
    1. Bernstein AM, Sun Q, Hu FB, Stampfer MJ, Manson JE, Willett WC. Major dietary protein sources and risk of coronary heart disease in women. Circulation. 2010;122(9):876–83.
    1. Rizza W, Veronese N, Fontana L. What are the roles of calorie restriction and diet quality in promoting healthy longevity?. Ageing Res Rev. 2014;13:38–45.
    1. Appleby PN, Key TJ. The long-term health of vegetarians and vegans. Proc Nutr Soc. 2016;75(3):287–93.
    1. Song M, Fung TT, Hu FB, Willett WC, Longo VD, Chan AT, Giovannucci EL. Association of animal and plant protein intake with all-cause and cause-specific mortality. JAMA Intern Med. 2016;176(10):1453–63.
    1. Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med. 2009;169(6):562–71.
    1. Alexander DD, Weed DL, Cushing CA, Lowe KA. Meta-analysis of prospective studies of red meat consumption and colorectal cancer. Eur J Cancer Prev. 2011;20(4):293–307.
    1. Steinbrecher A, Erber E, Grandinetti A, Kolonel LN, Maskarinec G. Meat consumption and risk of type 2 diabetes: the Multiethnic Cohort. Public Health Nutr. 2011;14(4):568–74.
    1. Sinha R. An epidemiologic approach to studying heterocyclic amines. Mutat Res. 2002;506-507:197–204.
    1. Gooderham NJ, Murray S, Lynch AM, Yadollahi-Farsani M, Zhao K, Rich K, Boobis AR, Davies DS. Assessing human risk to heterocyclic amines. Mutat Res. 1997;376(1-2):53–60.
    1. Sugimura T. Nutrition and dietary carcinogens. Carcinogenesis. 2000;21(3):387–95.
    1. Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH et al. .. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73.
    1. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA et al. .. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63.
    1. Longo VD, Panda S. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab. 2016;23(6):1048–59.
    1. Goldhamer A, Lisle D, Parpia B, Anderson SV, Campbell TC. Medically supervised water-only fasting in the treatment of hypertension. J Manipulative Physiol Ther. 2001;24(5):335–9.
    1. Goldhamer AC. Initial cost of care results in medically supervised water-only fasting for treating high blood pressure and diabetes. J Altern Complement Med. 2002;8(6):696–7.
    1. Michalsen A, Hoffmann B, Moebus S, Backer M, Langhorst J, Dobos GJ. Incorporation of fasting therapy in an integrative medicine ward: evaluation of outcome, safety, and effects on lifestyle adherence in a large prospective cohort study. J Altern Complement Med. 2005;11(4):601–7.
    1. Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG et al. .. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes. 2011;35(5):714–27.
    1. Florakis D, Diamanti-Kandarakis E, Katsikis I, Nassis GP, Karkanaki A, Georgopoulos N, Panidis D. Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24-week study. Int J Obes. 2008;32(4):692–9.
    1. Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S et al. .. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013;110(8):1534–47.
    1. Galea S, Tracy M. Participation rates in epidemiologic studies. Ann Epidemiol. 2007;17(9):643–53.
    1. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age- based disparities. JAMA. 2004;291(22):2720–6.
    1. Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M et al. .. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 2015;22(1):86–99.
    1. Cheng CW, Villani V, Buono R, Wei M, Kumar S, Yilmaz OH, Cohen P, Sneddon JB, Perin L, Longo VD. Fasting-mimicking diet promotes Ngn3-driven beta-cell regeneration to reverse diabetes. Cell. 2017;168(5):775–88.
    1. Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M et al. .. Fasting-mimicking diet reduces HO-1 to promote T cell-mediated tumor cytotoxicity. Cancer Cell. 2016;30(1):136–46.
    1. Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE et al. .. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep. 2016;15(10):2136–46.
    1. Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S et al. .. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377):pii: eaai8700.

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