Glycine supplementation extends lifespan of male and female mice
dc.contributor.author | Miller, Richard A. | |
dc.contributor.author | Harrison, David E. | |
dc.contributor.author | Astle, C. Michael | |
dc.contributor.author | Bogue, Molly A. | |
dc.contributor.author | Brind, Joel | |
dc.contributor.author | Fernandez, Elizabeth | |
dc.contributor.author | Flurkey, Kevin | |
dc.contributor.author | Javors, Martin | |
dc.contributor.author | Ladiges, Warren | |
dc.contributor.author | Leeuwenburgh, Christiaan | |
dc.contributor.author | Macchiarini, Francesca | |
dc.contributor.author | Nelson, James | |
dc.contributor.author | Ryazanov, Alexey G. | |
dc.contributor.author | Snyder, Jessica | |
dc.contributor.author | Stearns, Timothy M. | |
dc.contributor.author | Vaughan, Douglas E. | |
dc.contributor.author | Strong, Randy | |
dc.date.accessioned | 2019-05-31T18:28:04Z | |
dc.date.available | WITHHELD_14_MONTHS | |
dc.date.available | 2019-05-31T18:28:04Z | |
dc.date.issued | 2019-06 | |
dc.identifier.citation | Miller, Richard A.; Harrison, David E.; Astle, C. Michael; Bogue, Molly A.; Brind, Joel; Fernandez, Elizabeth; Flurkey, Kevin; Javors, Martin; Ladiges, Warren; Leeuwenburgh, Christiaan; Macchiarini, Francesca; Nelson, James; Ryazanov, Alexey G.; Snyder, Jessica; Stearns, Timothy M.; Vaughan, Douglas E.; Strong, Randy (2019). "Glycine supplementation extends lifespan of male and female mice." Aging Cell 18(3): n/a-n/a. | |
dc.identifier.issn | 1474-9718 | |
dc.identifier.issn | 1474-9726 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/149346 | |
dc.description.abstract | Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). Pooling across sex, glycine increased lifespan at each of the three independent sites, with significance at p = 0.01, 0.053, and 0.03, respectively. Glycine‐supplemented females were lighter than controls, but there was no effect on weight in males. End‐of‐life necropsies suggested that glycine‐treated mice were less likely than controls to die of pulmonary adenocarcinoma (p = 0.03). Of the 40 varieties of incidental pathology evaluated in these mice, none were increased to a significant degree by the glycine‐supplemented diet. In parallel analyses of the same cohort, we found no benefits from TM5441 (an inhibitor of PAI‐1, the primary inhibitor of tissue and urokinase plasminogen activators), inulin (a source of soluble fiber), or aspirin at either of two doses. Our glycine results strengthen the idea that modulation of dietary amino acid levels can increase healthy lifespan in mice, and provide a foundation for further investigation of dietary effects on aging and late‐life diseases. | |
dc.publisher | Wiley Periodicals, Inc. | |
dc.subject.other | life span | |
dc.subject.other | anti‐aging | |
dc.subject.other | longevity regulation | |
dc.title | Glycine supplementation extends lifespan of male and female mice | |
dc.type | Article | |
dc.rights.robots | IndexNoFollow | |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | |
dc.subject.hlbtoplevel | Health Sciences | |
dc.description.peerreviewed | Peer Reviewed | |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/149346/1/acel12953_am.pdf | |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/149346/2/acel12953.pdf | |
dc.identifier.doi | 10.1111/acel.12953 | |
dc.identifier.source | Aging Cell | |
dc.identifier.citedreference | Strong, R., Miller, R. A., Antebi, A., Astle, C. M., Bogue, M., Denzel, M. S., … Harrison, D. E. ( 2016 ). Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an alpha‐glucosidase inhibitor or a Nrf2‐inducer. Aging Cell, 15 ( 5 ), 872 – 884. https://doi.org/10.1111/acel.12496 | |
dc.identifier.citedreference | Guasch‐Ferré, M., Hruby, A., Toledo, E., Clish, C. B., Martínez‐González, M. A., Salas‐Salvadó, J., & Hu, F. B. ( 2016 ). Metabolomics in prediabetes and diabetes: A systematic review and meta‐analysis. Diabetes Care, 39 ( 5 ), 833 – 846. https://doi.org/10.2337/dc15-2251 | |
dc.identifier.citedreference | Harrison, D. E., Strong, R., Allison, D. B., Ames, B. N., Astle, C. M., Atamna, H., … Miller, R. A. ( 2014 ). Acarbose, 17‐alpha‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell, 13 ( 2 ), 273 – 282. https://doi.org/10.1111/acel.12170 | |
dc.identifier.citedreference | Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., … Miller, R. A. ( 2009 ). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460, 392 – 395. https://doi.org/10.1038/nature08221 | |
dc.identifier.citedreference | Hartiala, J. A., Tang, W. H., Wang, Z., Crow, A. L., Stewart, A. F., Roberts, R., … Allayee, H. ( 2016 ). Genome‐wide association study and targeted metabolomics identifies sex‐specific association of CPS1 with coronary artery disease. Nature Communications, 7, 10558. https://doi.org/10.1038/ncomms10558 | |
dc.identifier.citedreference | Khan, S. S., Shah, S. J., Klyachko, E., Baldridge, A. S., Eren, M., Place, A. T., … Vaughan, D. E. ( 2017 ). A null mutation in SERPINE1 protects against biological aging in humans. Science Advances, 3 ( 11 ), eaao1617. https://doi.org/10.1126/sciadv.aao1617 | |
dc.identifier.citedreference | Lieb, W., Larson, M. G., Benjamin, E. J., Yin, X., Tofler, G. H., Selhub, J., … Mitchell, G. F. ( 2009 ). Multimarker approach to evaluate correlates of vascular stiffness: The Framingham Heart Study. Circulation, 119 ( 1 ), 37 – 43. https://doi.org/10.1161/CIRCULATIONAHA.108.816108 | |
dc.identifier.citedreference | Lipman, R., Galecki, A., Burke, D. T., & Miller, R. A. ( 2004 ). Genetic loci that influence cause of death in a heterogeneous mouse stock. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59A, 977 – 983. | |
dc.identifier.citedreference | Luka, Z., Mudd, S. H., & Wagner, C. ( 2009 ). Glycine N‐methyltransferase and regulation of S‐adenosylmethionine levels. Journal of Biological Chemistry, 284 ( 34 ), 22507 – 22511. https://doi.org/10.1074/jbc.R109.019273 | |
dc.identifier.citedreference | Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., 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 ( 3 ), 119 – 125. https://doi.org/10.1111/j.1474-9726.2005.00152.x | |
dc.identifier.citedreference | Miller, R. A., & Chrisp, C. ( 2002 ). T cell subset patterns that predict resistance to spontaneous lymphoma, mammary adenocarcinoma, and fibrosarcoma in mice. The Journal of Immunology, 169, 1619 – 1625. https://doi.org/10.4049/jimmunol.169.3.1619 | |
dc.identifier.citedreference | Miller, R. A., Harrison, D. E., Astle, C. M., Fernandez, E., Flurkey, K., Han, M., … Strong, R. ( 2014 ). Rapamycin‐mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell, 13 ( 3 ), 468 – 477. https://doi.org/10.1111/acel.12194 | |
dc.identifier.citedreference | Orentreich, N., Matias, J. R., DeFelice, A., & Zimmerman, J. A. ( 1993 ). Low methionine ingestion by rats extends life span. Journal of Nutrition, 123, 269 – 274. | |
dc.identifier.citedreference | Osman, D., Ali, O., Obada, M., El‐Mezayen, H., & El‐Said, H. ( 2017 ). Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients. Biomedical Chromatography, 31 ( 6 ). https://doi.org/10.1002/bmc.3893 | |
dc.identifier.citedreference | Richie, J. P., Komninou, D., Leutzinger, Y., Kleinman, W., Orentreich, N., Malloy, V., & Zimmerman, J. A. ( 2004 ). Tissue glutathione and cysteine levels in methionine‐restricted rats. Nutrition, 20 ( 9 ), 800 – 805. https://doi.org/10.1016/j.nut.2004.05.009 | |
dc.identifier.citedreference | Richie, J. P., Leutzinger, Y., Parthasarathy, S., Malloy, V., Orentreich, N., & Zimmerman, J. A. ( 1994 ). Methionine restriction increases blood glutathione and longevity in F344 rats. The FASEB Journal, 8, 1302 – 1307. https://doi.org/10.1096/fasebj.8.15.8001743 | |
dc.identifier.citedreference | Rozan, P., Nejdi, A., Hidalgo, S., Bisson, J.‐F., Desor, D., & Messaoudi, M. ( 2008 ). Effects of lifelong intervention with an oligofructose‐enriched inulin in rats on general health and lifespan. British Journal of Nutrition, 100 ( 6 ), 1192 – 1199. https://doi.org/10.1017/S0007114508975607 | |
dc.identifier.citedreference | Schemmer, P., Zhong, Z., Galli, U., Wheeler, M. D., Xiangli, L. i., Bradford, B. U., … Thurman, R. G. ( 2013 ). Glycine reduces platelet aggregation. Amino Acids, 44 ( 3 ), 925 – 931. https://doi.org/10.1007/s00726-012-1422-8 | |
dc.identifier.citedreference | Snyder, J. M., Ward, J. M., & Treuting, P. M. ( 2016 ). Cause‐of‐death analysis in rodent aging studies. Veterinary Pathology, 53 ( 2 ), 233 – 243. https://doi.org/10.1177/0300985815610391 | |
dc.identifier.citedreference | Sobel, B. E., Lee, Y.‐H., Pratley, R. E., & Schneider, D. J. ( 2006 ). Increased plasminogen activator inhibitor type‐1 (PAI‐1) in the heart as a function of age. Life Sciences, 79 ( 17 ), 1600 – 1605. https://doi.org/10.1016/j.lfs.2006.05.011 | |
dc.identifier.citedreference | Song, C., Burgess, S., Eicher, J. D., O’Donnell, C. J., & Johnson, A. D. ( 2017 ). Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease. Journal of the American Heart Association, 6 ( 6 ), e004918. https://doi.org/10.1161/JAHA.116.004918 | |
dc.identifier.citedreference | Strong, R., Miller, R. A., Astle, C. M., Baur, J. A., de Cabo, R., Fernandez, E., … Harrison, D. E. ( 2013 ). Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium‐chain triglyceride oil on life span of genetically heterogeneous mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 68 ( 1 ), 6 – 16. https://doi.org/10.1093/gerona/gls070 | |
dc.identifier.citedreference | Strong, R., Miller, R. A., Astle, C. M., Floyd, R. A., Flurkey, K., Hensley, K. L., … Harrison, D. E. ( 2008 ). Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell, 7, 641 – 650. https://doi.org/10.1111/j.1474-9726.2008.00414.x | |
dc.identifier.citedreference | Sun, L., Sadighi Akha, A. A., Miller, R. A., & Harper, J. M. ( 2009 ). Life‐span extension in mice by preweaning food restriction and by methionine restriction in middle age. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 64 ( 7 ), 711 – 722. https://doi.org/10.1093/gerona/glp051 | |
dc.identifier.citedreference | Testa, R., Bonfigli, A. R., Salvioli, S., Invidia, L., Pierini, M., Sirolla, C., … Franceschi, C. ( 2009 ). The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI‐1 plasma levels in ageing. Mechanisms of Ageing and Development, 130 ( 8 ), 497 – 500. https://doi.org/10.1016/j.mad.2009.06.001 | |
dc.identifier.citedreference | Wang, C., Li, Q., Redden, D. T., Weindruch, R., & Allison, D. B. ( 2004 ). Statistical methods for testing effects on "maximum lifespan". Mechanisms of Ageing and Development, 125 ( 9 ), 629 – 632. https://doi.org/10.1016/j.mad.2004.07.003 | |
dc.identifier.citedreference | Wang, W., Wu, Z., Dai, Z., Yang, Y., Wang, J., & Wu, G. ( 2013 ). Glycine metabolism in animals and humans: Implications for nutrition and health. Amino Acids, 45 ( 3 ), 463 – 477. https://doi.org/10.1007/s00726-013-1493-1 | |
dc.identifier.citedreference | Wheeler, M. D., Ikejema, K., Enomoto, N., Stacklewitz, R. F., Seabra, V., Zhong, Z., … Thurman, R. G. ( 1999 ). Glycine: A new anti‐inflammatory immunonutrient. Cellular and Molecular Life Sciences, 56 ( 9–10 ), 843 – 856. | |
dc.identifier.citedreference | Wilkinson, J. E., Burmeister, L., Brooks, S. V., Chan, C.‐C., Friedline, S., Harrison, D. E., … Miller, R. A. ( 2012 ). Rapamycin slows aging in mice. Aging Cell, 11 ( 4 ), 675 – 682. https://doi.org/10.1111/j.1474-9726.2012.00832.x | |
dc.identifier.citedreference | Wolf, N. S., Giddens, W. E., & Martin, G. M. ( 1988 ). Life table analysis and pathologic observations in male mice of a long‐lived hybrid strain (A f X C57BL/6)F 1. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 43, B71 – B78. | |
dc.identifier.citedreference | Yamamoto, K., Shimokawa, T., Yi, H., Isobe, K.‐I., Kojima, T., Loskutoff, D. J., & Saito, H. ( 2002 ). Aging accelerates endotoxin‐induced thrombosis: Increased responses of plasminogen activator inhibitor‐1 and lipopolysaccharide signaling with aging. The American Journal of Pathology, 161 ( 5 ), 1805 – 1814. https://doi.org/10.1016/S0002-9440(10)64457-4 | |
dc.identifier.citedreference | Yi, N., Xu, S., & Allison, D. B. ( 2003 ). Bayesian model choice and search strategies for mapping interacting quantitative trait loci. Genetics, 165 ( 2 ), 867 – 883. | |
dc.identifier.citedreference | Zhong, Z., Wheeler, M. D., Li, X., Froh, M., Schemmer, P., Yin, M., … Lemasters, J. J. ( 2003 ). L‐Glycine: A novel antiinflammatory, immunomodulatory, and cytoprotective agent. Current Opinion in Clinical Nutrition and Metabolic Care, 6 ( 2 ), 229 – 240. https://doi.org/10.1097/00075197-200303000-00013 | |
dc.identifier.citedreference | Zimmerman, J. A., Malloy, V., Krajcik, R., & Orentreich, N. ( 2003 ). Nutritional control of aging. Experimental. Gerontology, 38 ( 1–2 ), 47 – 52. | |
dc.identifier.citedreference | Alarcon‐Aguilar, F. J., Almanza‐Perez, J., Blancas, G., Angeles, S., Garcia‐Macedo, R., Roman, R., & Cruz, M. ( 2008 ). Glycine regulates the production of pro‐inflammatory cytokines in lean and monosodium glutamate‐obese mice. European Journal of Pharmacology, 599 ( 1–3 ), 152 – 158. https://doi.org/10.1016/j.ejphar.2008.09.047 | |
dc.identifier.citedreference | Alessi, M. C., & Juhan‐Vague, I. ( 2006 ). PAI‐1 and the metabolic syndrome: Links, causes, and consequences. Arteriosclerosis, Thrombosis, and Vascular Biology, 26 ( 10 ), 2200 – 2207. https://doi.org/10.1161/01.ATV.0000242905.41404.68 | |
dc.identifier.citedreference | Boe, A. E., Eren, M., Murphy, S. B., Kamide, C. E., Ichimura, A., Terry, D., … Vaughan, D. E. ( 2013 ). Plasminogen activator inhibitor‐1 antagonist TM5441 attenuates Nomega‐nitro‐L‐arginine methyl ester‐induced hypertension and vascular senescence. Circulation, 128 ( 21 ), 2318 – 2324. https://doi.org/10.1161/CIRCULATIONAHA.113.003192 | |
dc.identifier.citedreference | Brind, J., Malloy, V., Augie, I., Caliendo, N., Vogelman, J. H., Zimmerman, J. A., & Orentreich, N. ( 2011 ). Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. The FASEB Journal, 25, 528. | |
dc.identifier.citedreference | Brown‐Borg, H. M., Rakoczy, S. G., Wonderlich, J. A., Rojanathammanee, L., Kopchick, J. J., Armstrong, V., & Raasakka, D. ( 2014 ). Growth hormone signaling is necessary for lifespan extension by dietary methionine. Aging Cell, 13 ( 6 ), 1019 – 1027. https://doi.org/10.1111/acel.12269 | |
dc.identifier.citedreference | Cruz, M., Maldonado‐Bernal, C., Mondragon‐Gonzalez, R., Sanchez‐Barrera, R., Wacher, N. H., Carvajal‐Sandoval, G., & Kumate, J. ( 2008 ). Glycine treatment decreases proinflammatory cytokines and increases interferon‐gamma in patients with type 2 diabetes. Journal of Endocrinological Investigation, 31 ( 8 ), 694 – 699. | |
dc.identifier.citedreference | Ding, Y., Svingen, G. F., Pedersen, E. R., Gregory, J. F., Ueland, P. M., Tell, G. S., & NygAard, O. K. ( 2015 ). Plasma glycine and risk of acute myocardial infarction in patients with suspected stable angina pectoris. Journal of the American Heart Association, 5 ( 1 ), e002621. https://doi.org/10.1161/JAHA.115.002621 | |
dc.identifier.citedreference | Eren, M., Boe, A. E., Murphy, S. B., Place, A. T., Nagpal, V., Morales‐Nebreda, L., … Vaughan, D. E. ( 2014 ). PAI‐1‐regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proceedings of the National Academy of Sciences of the United States of America, 111 ( 19 ), 7090 – 7095. https://doi.org/10.1073/pnas.1321942111 | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.