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Induction of autophagy by spermidine promotes longevity

Nature Cell Biology volume 11, pages 1305–1314 (2009)Cite this article

Abstract

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

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Figure 1: Application of spermidine extends the lifespan of yeast, flies and human immune cells, and inhibits oxidative stress in ageing mice.
Figure 2: Polyamine depletion shortens yeast chronological lifespan evoking markers of oxidative stress and necrosis.
Figure 3: Spermidine application suppresses necrotic cell death.
Figure 4: Lifespan extension by spermidine application is accompanied by epigenetic hypoacetylation of histone H3.
Figure 5: Spermidine-induced longevity is mediated by inhibition of HAT activity and correlates with upregulation of autophagy-related genes.
Figure 6: Autophagy is induced by spermidine and critical for maximal life span extension in yeast.
Figure 7: Autophagy is essential for spermidine-induced life span extension in flies and worms.

References

  1. Fabrizio, P. et al. Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. J. Cell Biol. 166, 1055–1067 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Herker, E. et al. Chronological aging leads to apoptosis in yeast. J. Cell Biol. 164, 501–507 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vicencio, J. M. et al. Senescence, apoptosis or autophagy? When a damaged cell must decide its path—a mini-review. Gerontology 54, 92–99 (2008).

    Article  PubMed  Google Scholar 

  4. Golstein, P. & Kroemer, G. Cell death by necrosis: towards a molecular definition. Trends Biochem. Sci. 32, 37–43 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Zong, W. X. & Thompson, C. B. Necrotic death as a cell fate. Genes Dev. 20, 1–15 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Imai, S., Armstrong, C. M., Kaeberlein, M. & Guarente, L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800 (2000).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Lamming, D. W. et al. HST2 mediates SIR2-independent life-span extension by calorie restriction. Science 309, 1861–1864 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Kaeberlein, M., Burtner, C. R. & Kennedy, B. K. Recent developments in yeast aging. PLoS Genet. 3, e84 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Longo, V. D. & Kennedy, B. K. Sirtuins in aging and age-related disease. Cell 126, 257–268 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Dang, W. et al. Histone H4 lysine 16 acetylation regulates cellular lifespan. Nature 459, 802–807 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Longo, V. D. & Finch, C. E. Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299, 1342–1346 (2003).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bonawitz, N. D., Chatenay-Lapointe, M., Pan, Y. & Shadel, G. S. Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab. 5, 265–277 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Galluzzi, L. et al. To die or not to die: that is the autophagic question. Curr. Mol. Med. 8, 78–91 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Jia, K. & Levine, B. Autophagy is required for dietary restriction-mediated life span extension in C. elegans. Autophagy 3, 597–599 (2007).

    Article  PubMed  Google Scholar 

  19. Scalabrino, G. & Ferioli, M. E. Polyamines in mammalian ageing: an oncological problem, too? A review. Mech. Ageing Dev. 26, 149–164 (1984).

    Article  CAS  PubMed  Google Scholar 

  20. Weinberger, M. et al. Apoptosis in budding yeast caused by defects in initiation of DNA replication. J. Cell Sci. 118, 3543–3553 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Allen, C. et al. Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures. J. Cell Biol. 174, 89–100 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Laun, P. et al. Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol. Microbiol. 39, 1166–1173 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Fabrizio, P., Pozza, F., Pletcher, S. D., Gendron, C. M. & Longo, V. D. Regulation of longevity and stress resistance by Sch9 in yeast. Science 292, 288–290 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11, 298–300 (1956).

    Article  CAS  PubMed  Google Scholar 

  25. Schraml, E. et al. Norepinephrine treatment and aging lead to systemic and intracellular oxidative stress in rats. Exp. Gerontol. 42, 1072–1078 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Artal-Sanz, M., Samara, C., Syntichaki, P. & Tavernarakis, N. Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans. J. Cell Biol. 173, 231–239 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Syntichaki, P., Samara, C. & Tavernarakis, N. The vacuolar H+-ATPase mediates intracellular acidification required for neurodegeneration in C. elegans. Curr. Biol. 15, 1249–1254 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Burtner, C. R., Murakami, C. J., Kennedy, B. K. & Kaeberlein, M. A molecular mechanism of chronological aging in yeast. Cell Cycle 8, 1256–1270 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Fabrizio, P. et al. Sir2 blocks extreme life-span extension. Cell 123, 655–667 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Burhans, W. C. & Weinberger, M. Acetic acid effects on aging in budding yeast: Are they relevant to aging in higher eukaryotes? Cell Cycle 8 (2009).

  31. Scaffidi, P., Misteli, T. & Bianchi, M. E. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191–195 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Weinberger, M. et al. DNA replication stress is a determinant of chronological lifespan in budding yeast. PLoS ONE 2, e748 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Duncan, E. M. et al. Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation. Cell 135, 284–294 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Howe, L. et al. Histone H3 specific acetyltransferases are essential for cell cycle progression. Genes Dev. 15, 3144–3154 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Winkler, G. S., Kristjuhan, A., Erdjument-Bromage, H., Tempst, P. & Svejstrup, J. Q. Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proc. Natl Acad. Sci. USA 99, 3517–3522 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hobbs, C. A., Paul, B. A. & Gilmour, S. K. Elevated levels of polyamines alter chromatin in murine skin and tumors without global changes in nucleosome acetylation. Exp. Cell Res. 290, 427–436 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Hobbs, C. A., Paul, B. A. & Gilmour, S. K. Deregulation of polyamine biosynthesis alters intrinsic histone acetyltransferase and deacetylase activities in murine skin and tumors. Cancer Res. 62, 67–74 (2002).

    CAS  PubMed  Google Scholar 

  38. Liu, B., Sutton, A. & Sternglanz, R. A yeast polyamine acetyltransferase. J. Biol. Chem. 280, 16659–16664 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Juhasz, G., Erdi, B., Sass, M. & Neufeld, T. P. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev. 21, 3061–3066 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tavernarakis, N., Pasparaki, A., Tasdemir, E., Maiuri, M. C. & Kroemer, G. The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy 4, 870–873 (2008).

    Article  CAS  PubMed  Google Scholar 

  41. Melendez, A. et al. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387–1391 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Orvedahl, A. & Levine, B. Eating the enemy within: autophagy in infectious diseases. Cell Death Differ. 16, 57-69 (2009).

  43. Hoyer-Hansen, M. & Jaattela, M. Autophagy: an emerging target for cancer therapy. Autophagy 4, 574–580 (2008).

    Article  PubMed  Google Scholar 

  44. Lambert, L. A. et al. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model. Cancer Res. 68, 7966–7974 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Lefranc, F., Facchini, V. & Kiss, R. Proautophagic drugs: a novel means to combat apoptosis-resistant cancers, with a special emphasis on glioblastomas. Oncologist 12, 1395–1403 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Franceschi, C. et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92–105 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Levine, B. & Kroemer, G. Autophagy in the pathogenesis of disease. Cell 132, 27–42 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Balasundaram, D., Tabor, C. W. & Tabor, H. Spermidine or spermine is essential for the aerobic growth of Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 88, 5872–5876 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gueldener, U., Heinisch, J., Koehler, G. J., Voss, D. & Hegemann, J. H. A second set of loxP marker cassettes for Cre-mediated multiple gene knockouts in budding yeast. Nucleic Acids Res. 30, e23 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Buttner, S. et al. Endonuclease G regulates budding yeast life and death. Mol. Cell 25, 233–246 (2007).

    Article  PubMed  Google Scholar 

  51. Lotze, M. T. & Tracey, K. J. High-mobility group Box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Rev. Immunol. 5, 331–342 (2005).

    Article  CAS  Google Scholar 

  52. Kirisako, T. et al. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J. Cell Biol. 147, 435–446 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Noda, T., Matsuura, A., Wada, Y. & Ohsumi, Y. Novel system for monitoring autophagy in the yeast Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 210, 126–132 (1995).

    Article  CAS  PubMed  Google Scholar 

  54. Vermes, I., Haanen, C., Steffens-Nakken, H. & Reutelingsperger, C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J. Immunol. Methods 184, 39–51 (1995).

    Article  CAS  PubMed  Google Scholar 

  55. Criollo, A. et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 14, 1029–1039 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Ellman, G. L. Tissue sulfhydryl groups. Arch. Biochem. Biophys. 82, 70–77 (1959).

    Article  CAS  PubMed  Google Scholar 

  57. Riener, C. K., Kada, G. & Gruber, H. J. Quick measurement of protein sulfhydryls with Ellman's reagent and with 4, 4′-dithiodipyridine. Anal. Bioanal. Chem. 373, 266–276 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Samara, C., Syntichaki, P. & Tavernarakis, N. Autophagy is required for necrotic cell death in Caenorhabditis elegans. Cell Death Differ. 15, 105–112 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Minocha, R., Shortle, W. C., Long, S. L. & Minocha, S. C. A rapid and reliable procedure for extraction of cellular polyamines and inorganic ions from plant tissues. J. Plant Growth Regul. 13, 187–193 (1994).

    Article  CAS  Google Scholar 

  61. Gianotti, V. et al. A new hydrophilic interaction liquid chromatography tandem mass spectrometry method for the simultaneous determination of seven biogenic amines in cheese. J. Chromatogr. A 1185, 296–300 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Fahrenkrog, B., Hurt, E. C., Aebi, U. & Pante, N. Molecular architecture of the yeast nuclear pore complex: localization of Nsp1p subcomplexes. J. Cell Biol. 143, 577–588 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wu, Z., Irizarry, R. A., Gentleman, R., Martinez-Murillo, F. & Spencer, F. A model-based background adjustment for oligonucleotide expression arrays. J. Am. Stat. Assoc. 99, 909–918 (2004).

    Article  Google Scholar 

  64. Rainer, J., Sanchez-Cabo, F., Stocker, G., Sturn, A. & Trajanoski, Z. CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis. Nucleic Acids Res. 34, W498–W503 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Saeed, A. I. et al. TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34, 374–378 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Rozen, S. & Skaletsky, H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 132, 365–386 (2000).

    CAS  PubMed  Google Scholar 

  67. Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-δ δ C(T)) method. Methods 25, 402–408 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Strahl-Bolsinger, S., Hecht, A., Luo, K. & Grunstein, M. SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast. Genes Dev. 11, 83–93 (1997).

    Article  CAS  PubMed  Google Scholar 

  69. Evans, E., Sugawara, N., Haber, J. E. & Alani, E. The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Mol. Cell 5, 789–799 (2000).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Ulrike Potocnik, Silvia Dichtinger, Arno Absenger and Elfgard Heintz for assistance. We are grateful to the Austrian Science Fund FWF (Austria) for grant S-9304-B05 (to F.M., S.B. and D.C.-G.), grant S-9303-B05 (to K.-U.F. and H.K.), grant LIPOTOX (to F.M. and S.B.), and grant S-9301-B05 (to B.G.-L.) and to the European Commission for project TransDeath (to K.-U.F. and C.R.), project APOSYS (to F.M., T.E. and G.K.) and project Lifespan (FP6 036894 to B.G.-L.). We are grateful to the Austrian Science Fund FWF (Vienna, Austria) for grants S9302-B05 (to M.B.) and to the European Commission (Brussels, Europe) for project MIMAGE (contract no. 512020; to M.B.).

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  1. Nadege Minois

    Present address: Current address: School of Biology, University of St Andrews, St Andrews, Scotland, Fife KY16 9AJ, UK.,

Authors and Affiliations

  1. Institute of Molecular Biosciences, University of Graz, Graz, 8010, Austria

    Tobias Eisenberg, Heide Knauer, Alexandra Schauer, Sabrina Büttner, Christoph Ruckenstuhl, Didac Carmona-Gutierrez, Julia Ring, Sabrina Schroeder, Lucia Antonacci, Heike Fussi, Kai-Uwe Fröhlich & Frank Madeo

  2. Institute of Medical Technologies and Health Management, Joanneum Research, Graz, Austria

    Christoph Magnes & Frank Sinner

  3. Research Institute of Molecular Pathology (IMP), Vienna, Austria

    Luiza Deszcz, Regina Hartl & Nadege Minois

  4. Institute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna, Austria

    Luiza Deszcz, Regina Hartl & Nadege Minois

  5. Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Vienna, Austria

    Elisabeth Schraml

  6. INSERM, U848,

    Alfredo Criollo & Guido Kroemer

  7. Villejuif, 94805, France

    Alfredo Criollo & Guido Kroemer

  8. Institut Gustave Roussy, Villejuif, 94805, France

    Alfredo Criollo & Guido Kroemer

  9. University Paris Sud, Paris-11, Villejuif, 94805, France

    Alfredo Criollo & Guido Kroemer

  10. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, 70013, Crete, Greece

    Evgenia Megalou & Nektarios Tavernarakis

  11. Institute for Biomedical Ageing Research, Austrian Academy of Sciences, Innsbruck, 6020, Austria

    Daniela Weiskopf & Beatrix Grubeck-Loebenstein

  12. Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg, 5020, Austria

    Peter Laun, Gino Heeren & Michael Breitenbach

  13. Gladstone Institute of Virology and Immunology, San Francisco, 94158, CA, USA

    Eva Herker

  14. M.E. Mueller Institute for Structural Biology, Biozentrum, University of Basel, Basel, 4056, Switzerland

    Birthe Fahrenkrog

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Contributions

T.E., G.K. and F.M. designed and organized this study and wrote the manuscript. T.E. performed the largest part of the yeast and mouse experiments and contributed significantly to the fly and PBMC cell culture data. H.K., A.S., S.B., C.R., D.C-G., J.R., S.S., H.F., L.A. and B.A. contributed to the yeast experiments. C.M. and F.S. performed polyamine measurements by MassSpec. L.D., R.H. and N.M. performed the fly experiments. E.S. contributed to mouse data. A.C. performed HELA cell culture experiments. E.M. and N.T. contributed the worm data. D.W. and B.G-L. performed PBMC experiments. P.L., G.H. and M.B. determined yeast replicative life spans. N.M., E.H., K.-U.F., S.B., C.R. and D.C-G. contributed with decisive discussions and helped to design experiments.

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Correspondence to Guido Kroemer or Frank Madeo.

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Eisenberg, T., Knauer, H., Schauer, A. et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol 11, 1305–1314 (2009). https://doi.org/10.1038/ncb1975

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