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Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats

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Abstract

Dietary methionine restriction (MR) has been found to enhance longevity across many species. We hypothesized that MR might enhance longevity in part by delaying or inhibiting age-related disease processes. To this end, male Fischer 344 rats were fed control (CF, 0.86% methionine) or MR (0.17% methionine) diets throughout their life until sacrifice at approximately 30 months of age, and histopathology was performed to identify the incidence and progression of two important aging-related pathologies, namely, chronic progressive nephropathy (CPN) and testicular tumorigenesis. Although kidney pathology was observed in 87% CF rats and CPN in 62% of CF animals, no evidence of kidney disease was observed in MR rats. Consistent with the absence of renal pathology, urinary albumin levels were lower in the MR group compared to controls throughout the study, with over a six-fold difference between the groups at 30 months of age. Biomarkers associated with renal disease, namely, clusterin, cystatin C, and β-2 microglobulin, were reduced following 18 months of MR. A reduction in testicular tumor incidence from 88% in CF to 22% in MR rats was also observed. These results suggest that MR may lead to metabolic and cellular changes providing protection against age-related diseases.

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References

  • Ables GP, Perrone CE, Orentreich D, Orentreich N (2012) Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density. PLoS One 7:e51357

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ables GP, Ouattara A, Hampton TG, Cooke D, Perodin F, Augie I, Orentreich DS (2015) Dietary methionine restriction in mice elicits an adaptive cardiovascular response to hyperhomocysteinemia. Sci Rep 5:8886

    PubMed  PubMed Central  Google Scholar 

  • Alt JM, Hackbarth H, Deerberg F, Stolte H (1980) Proteinuria in rats in relation to age-dependent renal changes. Lab Anim 14:95–101

    CAS  PubMed  Google Scholar 

  • Ames BN, Gold LS (1991) Endogenous mutagens and the causes of aging and cancer. Mutat Res 250:3–16

    CAS  PubMed  Google Scholar 

  • Anderson S, Brenner BM (1986) Effects of aging on the renal glomerulus. Am J Med 80:435–442

    CAS  PubMed  Google Scholar 

  • Bertani T, Zoja C, Abbate M, Rossini M, Remuzzi G (1989) Age-related nephropathy and proteinuria in rats with intact kidneys exposed to diets with different protein content. Lab Investig 60:196–204

    CAS  PubMed  Google Scholar 

  • Breillout F, Hadida F, Echinard-Garin P, Lascaux V, Poupon MF (1987) Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet. Anticancer Res 7:861–867

    CAS  PubMed  Google Scholar 

  • Breillout F, Antoine E, Poupon MF (1990) Methionine dependency of malignant tumors: a possible approach for therapy. J Natl Cancer Inst 82:1628–1632

    CAS  PubMed  Google Scholar 

  • Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, López-Torres M, Pamplona R, Barja G (2009) Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuvenation Res 12:421–434

    CAS  PubMed  Google Scholar 

  • Cioni G, Marcucci R, Gori AM, Valente S, Giglioli C, Gensini GF, Abbate R, Boddi M (2016) Increased homocysteine and lipoprotein(a) levels highlight systemic atherosclerotic burden in patients with a history of acute coronary syndromes. J Vasc Surg 64:163–170

    PubMed  Google Scholar 

  • Coleman GL, Barthold W, Osbaldiston GW, Foster SJ, Jonas AM (1977) Pathological changes during aging in barrier-reared Fischer 344 male rats. J Gerontol 32:258–278

    CAS  PubMed  Google Scholar 

  • Cooke D, Ouattara A, Ables GP (2018) Dietary methionine restriction modulates renal response and attenuates kidney injury in mice. FASEB J 32:693–702

    CAS  PubMed  Google Scholar 

  • Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141:2608–2613

    CAS  PubMed  Google Scholar 

  • Dayal S, Chauhan AK, Jensen M, Leo L, Lynch CM, Faraci FM, Kruger WD, Lentz SR (2012) Paradoxical absence of a prothrombotic phenotype in a mouse model of severe hyperhomocysteinemia. Blood 119:3176–3183

    CAS  PubMed  PubMed Central  Google Scholar 

  • Diamond JR (1989) Hyperlipidemia of nephrosis: pathophysiologic role in progressive glomerular disease. Am J Med 87:25N–29N

    CAS  PubMed  Google Scholar 

  • Dodane V, Chevalier J, Bariety J, Pratz J, Corman B (1991) Longitudinal study of solute excretion and glomerular ultrastructure in an experimental model of aging rats free of kidney disease. Lab Investig 64:377–391

    CAS  PubMed  Google Scholar 

  • Dong Z, Sinha R, Richie JP Jr (2018) Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications. Ann N Y Acad Sci 1418:44–55

    CAS  PubMed  Google Scholar 

  • Elshorbagy AK, Valdivia-Garcia M, Refsum H, Smith AD, Mattocks DA, Perrone CE (2010) Sulfur amino acids in methionine-restricted rats: hyperhomocysteinemia. Nutrition 26:1201–1214

    CAS  PubMed  Google Scholar 

  • Epner DE (2001) Can dietary methionine restriction increase the effectiveness of chemotherapy in treatment of advanced cancer? J Am Coll Nutr 20:443S–449S

    CAS  PubMed  Google Scholar 

  • Everitt AV, Porter BD, Wyndham JR (1982) Effects of caloric intake and dietary composition on the development of proteinuria, age-associated renal disease and longevity in the male rat. Gerontology 28:168–175

    CAS  PubMed  Google Scholar 

  • Friend PS, Fernandes G, Good RA, Michael AF, Yunis EJ (1978) Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse. Lab Investig 38:629–632

    CAS  PubMed  Google Scholar 

  • Goodman DG, Ward JM, Squire RA, Chu KC, Linhart MS (1979) Neoplastic and nonneoplastic lesions in aging F344 rats. Toxicol Appl Pharmacol 48:237–248

    CAS  PubMed  Google Scholar 

  • Goseki N, Yamazaki S, Shimojyu K, Kando F, Maruyama M, Endo M, Koike M, Takahashi H (1995) Synergistic effect of methionine-depleting total parenteral nutrition with 5-fluorouracil on human gastric cancer: a randomized, prospective clinical trial. Jpn J Cancer Res 86:484–489

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grant L, Lees EK, Forney LA, Mody N, Gettys T, Brown PA, Wilson HM, Delibegovic M (2016) Methionine restriction improves renal insulin signalling in aged kidneys. Mech Ageing Dev 157:35–43

    CAS  PubMed  Google Scholar 

  • Gray JE, van Zwieten MJ, Hollander CF (1982) Early light microscopic changes in chronic progressive nephrosis in several strains of aging laboratory rats. J Gerontol 37:142–150

    CAS  PubMed  Google Scholar 

  • Guo HY, Herrera H, Groce A, Hoffman RM (1993a) Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res 53:2479–2483

    CAS  PubMed  Google Scholar 

  • Guo HY, Lishko VK, Herrera H, Groce A, Kubota T, Hoffman RM (1993b) Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Cancer Res 53:5676–5679

    CAS  PubMed  Google Scholar 

  • Hard GC, Johnson KJ, Cohen SM (2009) A comparison of rat chronic progressive nephropathy with human renal disease-implications for human risk assessment. Crit Rev Toxicol 39:332–346

    PubMed  Google Scholar 

  • Hasek BE, Stewart LK, Henagan TM, Boudreau A, Lenard NR, Black C, Shin J, Huypens P, Malloy VL, Plaisance EP, Krajcik RA, Orentreich N, Gettys TW (2010) Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Am J Phys Regul Integr Comp Phys 299:R728–R739

    CAS  Google Scholar 

  • Haseman JK, Arnold J, Eustis SL (1990) Thirty-five tumor incidences in Fischer 344 rats: NTP historical data. In: Boorman GA, Eustis SL, Montgomery C, Elwell M (eds) Pathology of the F344 rat. Academic Press, San Diego, pp 555–564

    Google Scholar 

  • Hens JR, Sinha I, Perodin F, Cooper T, Sinha R, Plummer J, Perrone CE, Orentreich D (2016) Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice. BMC Cancer 16:349

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988) The influence of dietary protein source on longevity and age-related disease processes of Fischer rats. J Gerontol 43:5–12

    Google Scholar 

  • Johnson JE, Johnson FB (2014) Methionine restriction activates the retrograde response and confers both stress tolerance and lifespan extension to yeast, mouse and human cells. PLoS One 9:e97729

    PubMed  PubMed Central  Google Scholar 

  • Judde JG, Ellis M, Frost P (1989) Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells. Cancer Res 49:4859–4865

    CAS  PubMed  Google Scholar 

  • Kane AE, Gregson E, Theou O, Rockwood K, Howlett SE (2017) The association between frailty, the metabolic syndrome, and mortality over the lifespan. Geroscience 39:221–229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klahr S (1989) Effects of protein intake on the progression of renal disease. Annu Rev Nutr 9:87–108

    CAS  PubMed  Google Scholar 

  • Kokkinakis DM, Schold SC Jr, Hori H, Nobori T (1997) Effect of long-term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice. Nutr Cancer 29:195–204

    CAS  PubMed  Google Scholar 

  • Komninou D, Leutzinger Y, Reddy BS, Richie JP Jr (2006) Methionine restriction inhibits colon carcinogenesis. Nutr Cancer 54:202–208

    CAS  PubMed  Google Scholar 

  • Koshiji M, Ogura E, Takada H, Kawanishi H, Ikehara S, Hioki K (1998) Clinicopathologic and immunohistochemical analyses in lung metastasis of colorectal carcinoma. Oncol Rep 5:811–815

    CAS  PubMed  Google Scholar 

  • Lang CA, Naryshkin S, Schneider DL, Mills BJ, Lindeman RD (1992) Low blood glutathione levels in healthy aging adults. J Lab Clin Med 120:720–725

    CAS  PubMed  Google Scholar 

  • Lee BC, Kaya A, Ma S, Kim G, Gerashchenko MV, Yim SH, Hu Z, Harshman LG, Gladyshev VN (2014) Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status. Nat Commun 5:3592

    PubMed  PubMed Central  Google Scholar 

  • Lees EK, Krol E, Grant L, Shearer K, Wyse C, Moncur E, Bykowska AS, Mody N, Gettys TW, Delibegovic M (2014) Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21. Aging Cell 13:817–827

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lees EK, Krol E, Shearer K, Mody N, Gettys TW, Delibegovic M (2015) Effects of hepatic protein tyrosine phosphatase 1B and methionine restriction on hepatic and whole-body glucose and lipid metabolism in mice. Metabolism 64:305–314

    CAS  PubMed  Google Scholar 

  • Lewis KN, Rubinstein ND, Buffenstein R (2018) A window into extreme longevity; the circulating metabolomic signature of the naked more-rat, a mammal that shows negligible senescence. Geroscience 40:105–121

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lim BJ, Yang HC, Fogo AB (2014) Animal models of regression/progression of kidney disease. Drug Discov Today Dis Model 11:45–51

    Google Scholar 

  • Lupia E, Elliot SJ, Lenz O, Zheng F, Hattori M, Striker GE, Striker LJ (1999) IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy. Diabetes 48:1638–1644

    CAS  PubMed  Google Scholar 

  • Lupton JR, Quispe R, Kulkarni K, Martin SS, Jones SR (2016) Serum homocysteine is not independently associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-21) study. Atherosclerosis 249:59–64

    CAS  PubMed  Google Scholar 

  • Ma S, Zhang H, Sun W, Gong H, Wang Y, Ma C, Wang J, Cao C, Yang X, Tian J, Jiang Y (2013) Hyperhomocysteinemia induces cardiac injury by up-regulation of p53-dependent Noxa and Bax expression through the p53 DNA methylation in ApoE(-/-) mice. Acta Biochim Biophys Sin Shanghai 45:391–400

    CAS  PubMed  Google Scholar 

  • Maddineni S, Nichenametla S, Sinha R, Wilson RP, Richie JP Jr (2013) Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat. Exp Biol Med (Maywood) 238:392–399

    Google Scholar 

  • Maeda H, Gleiser CA, Masoro EJ, Murata I, McMahan CA, Yu BP (1985) Nutritional influences on aging of Fischer 344 rats: II. Pathology. J Gerontol 40:671–688

    CAS  PubMed  Google Scholar 

  • Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N (2006) Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Aging Cell 5:305–314

    CAS  PubMed  Google Scholar 

  • Masoro EJ, Iwasaki K, Gleiser CA, McMahan CA, Seo EJ, Yu BP (1989) Dietary modulation of the progression of nephropathy in aging rats: an evaluation of the importance of protein. Am J Clin Nutr 49:1217–1227

    CAS  PubMed  Google Scholar 

  • Matsumoto N, Ishimura E, Taniwaki H, Emoto M, Shoji T, Kawagishi T, Inaba M, Nishizawa Y (2000) Diabetes mellitus worsens intrarenal hemodynamic abnormalities in nondialyzed patients with chronic renal failure. Nephron 86:44–51

    CAS  PubMed  Google Scholar 

  • Mecham JO, Rowitch D, Wallace CD, Stern PH, Hoffman RM (1983) The metabolic defect of methionine dependence occurs frequently in human tumor cell lines. Biochem Biophys Res Commun 117:429–434

    CAS  PubMed  Google Scholar 

  • Meigs JB (2002) Epidemiology of the metabolic syndrome. Am J Manag Care 8:S283–S292

    PubMed  Google Scholar 

  • Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M (2005) 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 4:119–125

    CAS  PubMed  Google Scholar 

  • Mullin JM, Skrovanek SM, Ramalingam A, DiGuilio KM, Valenzano MC (2016) Methionine restriction fundamentally supports health by tightening epithelial barriers. Ann N Y Acad Sci 1363:59–67

    CAS  PubMed  Google Scholar 

  • Murakami K, Kondo T, Ohtsuka Y, Fujiwara Y, Shimada M, Kawakami Y (1989) Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism 38:753–758

    CAS  PubMed  Google Scholar 

  • Nakatsuji S, Yamate J, Sakuma S (1998) Macrophages, myofibroblasts, and extracellular matrix accumulation in interstitial fibrosis of chronic progressive nephropathy in aged rats. Vet Pathol 35:352–360

    CAS  PubMed  Google Scholar 

  • Olecka M, Huse K, Platzer M (2018) The high degree of cystathionine β-synthase (CBS) activation by S-adenosylmethionine (SAM) may explain naked mole-rat's distinct methionine metabolite profile compared to mouse. Geroscience 40:359–360

    PubMed  PubMed Central  Google Scholar 

  • Orentreich N, Matias JR, DeFelice A, Zimmerman JA (1993) Low methionine ingestion by rats extends life span. J Nutr 123:269–274

    CAS  PubMed  Google Scholar 

  • Ouattara A, Cooke D, Gopalakrishnan R, Huang TH, Ables GP (2016) Methionine restriction alters bone morphology and affects osteoblast differentiation. Bone Rep 5:33–42

    PubMed  PubMed Central  Google Scholar 

  • Perrone CE, Mattocks DA, Jarvis-Morar M, Plummer JD, Orentreich N (2010) Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats. Metabolism 59:1000–1011

    CAS  PubMed  Google Scholar 

  • Pollak M (2000) Insulin-like growth factor physiology and cancer risk. Eur J Cancer 36:1224–1228

    CAS  PubMed  Google Scholar 

  • Prisco M, Romano G, Peruzzi F, Valentinis B, Baserga R (1999) Insulin and IGF-I receptors signaling in protection from apoptosis. Horm Metab Res 31:80–89

    CAS  PubMed  Google Scholar 

  • Rao MS, Subbarao V, Yeldandi AV, Reddy JK (1992) Inhibition of spontaneous testicular Leydig cell tumor development in F-344 rats by dehydroepiandrosterone. Cancer Lett 65:123–126

    CAS  PubMed  Google Scholar 

  • Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 8:1302–1307

    CAS  PubMed  Google Scholar 

  • Ruiz MC, Ayala V, Portero-Otin M, Requena JR, Barja G, Pamplona R (2005) Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals. Mech Ageing Dev 126:1106–1114

    CAS  PubMed  Google Scholar 

  • Sanz A, Caro P, Ayala V, Portero-Otin M, Pamplona R, Barja G (2006) Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins. FASEB J 20:1064–1073

    CAS  PubMed  Google Scholar 

  • Schwartz AG, Hard GC, Pashko LL, Abou-Gharbia M, Swern D (1981) Dehydroepiandrosterone: an anti-obesity and anti-carcinogenic agent. Nutr Cancer 3:46–53

    CAS  PubMed  Google Scholar 

  • Sinha R, Cooper TK, Rogers CJ, Sinha I, Turbitt WJ, Calcagnotto A, Perrone CE, Richie JP Jr (2014) Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice. Prostate 74:1663–1673

    CAS  PubMed  Google Scholar 

  • Stern JS, Gades MD, Wheeldon CM, Borchers AT (2001) Calorie restriction in obesity: prevention of kidney disease in rodents. J Nutr 131:913S–917S

    CAS  PubMed  Google Scholar 

  • Sugimura T, Birnbaum SM, Winitz M, Greenstein JP (1959) Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid. Arch Biochem Biophys 81:448–455

    CAS  PubMed  Google Scholar 

  • Sun L, Sadighi Akha AA, Miller RA, Harper JM (2009) Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J Gerontol A Biol Sci Med Sci 64:711–722

    PubMed  Google Scholar 

  • Tan Y, Xu M, Guo H, Sun X, Kubota T, Hoffman RM (1996) Anticancer efficacy of methioninase in vivo. Anticancer Res 16:3931–3936

    CAS  PubMed  Google Scholar 

  • Toth LA (2000) Defining the moribund condition as an experimental endpoint for animal research. ILAR J 41:72–79

    CAS  PubMed  Google Scholar 

  • Van Liew JB, Davis FB, Davis PJ, Noble B, Bernardis LL (1992) Calorie restriction decreases microalbuminuria associated with aging in barrier-raised Fischer 344 rats. Am J Phys 263:F554–F561

    Google Scholar 

  • Weaver RN, Gray JE, Schultz JR (1975) Urinary proteins in Sprague-Dawley rats with chronic progressive nephrosis. Lab Anim Sci 25:705–710

    CAS  PubMed  Google Scholar 

  • Weindruch R, Walford RL (1988) The Retardation of Aging and Disease by Dietary Restriction. Charles C Thomas, Springfield, Illinois

    Google Scholar 

  • Yang CW, Striker LJ, Kopchick JJ, Chen WY, Pesce CM, Peten EP, Striker GE (1993) Glomerulosclerosis in mice transgenic for native or mutated bovine growth hormone gene. Kidney Int Suppl 39:S90–S94

    CAS  PubMed  Google Scholar 

  • Yoshioka T, Wada T, Uchida N, Maki H, Yoshida H, Ide N, Kasai H, Hojo K, Shono K, Maekawa R, Yagi S, Hoffman RM, Sugita K (1998) Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase. Cancer Res 58:2583–2587

    CAS  PubMed  Google Scholar 

  • Yu BP, Masoro EJ, Murata I, Bertrand HA, Lynd FT (1982) Life span study of SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass and disease. J Gerontol 37:130–141

    CAS  PubMed  Google Scholar 

  • Zimmerman JA, Malloy V, Krajcik R, Orentreich N (2003) Nutritional control of aging. Exp Gerontol 38:47–52

    CAS  PubMed  Google Scholar 

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Acknowledgments

Authors would like to thank Dr. Abraham Rivenson, at American Health Foundation, Valhalla, NY for performing the histopathological examination on rat tissues in a blinded manner.

Dedication

We dedicate this paper to the memory of Norman Orentreich, MD. Dr. Orentreich was the first to describe methionine restriction as a means to extend lifespan and promote healthy aging. His commitment to the study of aging continues to inspire us as we move forward in our research.

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Authors and Affiliations

  1. Technological Educational Institute of Thessaloniki, Thessaloniki, Greece

    Despina Komninou

  2. Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, NY, 10516, USA

    Virginia L. Malloy & Jay A. Zimmerman

  3. Department of Biochemistry and Molecular Biology, Penn State Cancer Institute, Penn State University College of Medicine, 500 University Dr., Hershey, PA, 17033, USA

    Raghu Sinha

  4. Department of Public Health Sciences, Penn State Cancer Institute, Penn State University College of Medicine, 500 University Dr., Hershey, PA, 17033, USA

    John P. Richie Jr

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  1. Despina Komninou
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  2. Virginia L. Malloy
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  4. Raghu Sinha
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  5. John P. Richie Jr
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Correspondence to Raghu Sinha or John P. Richie Jr.

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Komninou, D., Malloy, V.L., Zimmerman, J.A. et al. Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats. GeroScience 42, 287–297 (2020). https://doi.org/10.1007/s11357-019-00129-4

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