Skip to main content
SpringerLink
Log in

Monitoring Nutrient Signaling Through the Longevity Protein p66SHC1

  • Protocol
  • First Online:
Cell Senescence

Part of the book series: Methods in Molecular Biology ((MIMB,volume 965))

  • 6661 Accesses

Abstract

Nutrient availability and nutrient-dependent biochemical signals represent major determinants of cellular senescence and organismal aging. The present chapter describes simple procedures to reliably evaluate the response of cultured cell to nutrients through the longevity protein p66SHC1 and the mTOR/S6K cascade, which might be used to study cellular senescence and its chemical modulation by pharmaceutical agents in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Jasper H, Jones DL (2010) Metabolic regulation of stem cell behavior and implications for aging. Cell Metab 12:561–565

    Article  PubMed  CAS  Google Scholar 

  2. Zoncu R, Efeyan A, Sabatini DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12:21–35

    Article  PubMed  CAS  Google Scholar 

  3. Sinclair DA (2005) Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev 126:987–1002

    Article  PubMed  CAS  Google Scholar 

  4. Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309–313

    Article  PubMed  CAS  Google Scholar 

  5. Koch OR, Fusco S, Ranieri SC, Maulucci G, Palozza P, Larocca LM, Cravero AA, Farre SM, De Spirito M, Galeotti T, Pani G (2008) Role of the life span determinant P66(shcA) in ethanol-induced liver damage. Lab Invest J Tech Meth Pathol 88:750–760

    Google Scholar 

  6. Cosentino F, Francia P, Camici GG, Pelicci PG, Luscher TF, Volpe M (2008) Final common molecular pathways of aging and cardiovascular disease: role of the p66Shc protein. Arterioscler Thromb Vasc Biol 28:622–628

    Article  PubMed  CAS  Google Scholar 

  7. Ranieri SC, Fusco S, Panieri E, Labate V, Mele M, Tesori V, Ferrara AM, Maulucci G, De Spirito M, Martorana GE, Galeotti T, Pani G (2010) Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance. Proc Natl Acad Sci USA 107:13420–13425

    Article  PubMed  CAS  Google Scholar 

  8. Berniakovich I, Trinei M, Stendardo M, Migliaccio E, Minucci S, Bernardi P, Pelicci PG, Giorgio M (2008) p66Shc-generated oxidative signal promotes fat accumulation. J Biol Chem 283:34283–34293

    Article  PubMed  CAS  Google Scholar 

  9. Pinton P, Rimessi A, Marchi S, Orsini F, Migliaccio E, Giorgio M, Contursi C, Minucci S, Mantovani F, Wieckowski MR, Del Sal G, Pelicci PG, Rizzuto R (2007) Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315:659–663

    Article  PubMed  CAS  Google Scholar 

  10. Um SH, D’Alessio D, Thomas G (2006) Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab 3:393–402

    Article  PubMed  CAS  Google Scholar 

  11. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395

    PubMed  CAS  Google Scholar 

  12. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326:140–144

    Article  PubMed  CAS  Google Scholar 

  13. Panieri E, Toietta G, Mele M, Labate V, Ranieri SC, Fusco S, Tesori V, Antonini A, Maulucci G, De Spirito M, Galeotti T, Pani G (2010) Nutrient withdrawal rescues growth factor-deprived cells from mTOR-dependent damage. Aging 2:487–503

    PubMed  CAS  Google Scholar 

  14. Demidenko ZN, Blagosklonny MV (2008) Growth stimulation leads to cellular senescence when the cell cycle is blocked. Cell Cycle 7:3355–3361

    Article  PubMed  CAS  Google Scholar 

  15. Chen C, Liu Y, Liu R, Ikenoue T, Guan KL, Liu Y, Zheng P (2008) TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 205:2397–2408

    Article  PubMed  CAS  Google Scholar 

  16. Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E, Milia E, Padura IM, Raker VA, Maccarana M, Petronilli V, Minucci S, Bernardi P, Lanfrancone L, Pelicci PG (2002) A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872–3878

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC grant IG8634/2009), by the Italian Ministry of University/Catholic University (linea D1, MIUR ex 60%) and by Italian Ministry of University, PRIN 2008, grant 2008T7WRTM_003.

Author information

Authors and Affiliations

  1. Clinical Chemistry, Laboratory and Endocrinology Unit, Departement of Laboratory Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy

    Sofia Chiatamone Ranieri

  2. Institute of General Pathology, Catholic University Medical School, Rome, Italy

    Giovambattista Pani

Authors
  1. Sofia Chiatamone Ranieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovambattista Pani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovambattista Pani .

Editor information

Editors and Affiliations

  1. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif, 94085, France

    Lorenzo Galluzzi

  2. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif CEDEX, 94085, France

    Ilio Vitale

  3. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif CEDEX, 94085, France

    Oliver Kepp

  4. Institut Gustave Roussy (IGR), Pavillon de Recherche 1, INSERM, U848, rue Camille-Desmoulins 39, Villejuif, 94805, France

    Guido Kroemer

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Busincess Media, LLC

About this protocol

Cite this protocol

Ranieri, S.C., Pani, G. (2013). Monitoring Nutrient Signaling Through the Longevity Protein p66SHC1 . In: Galluzzi, L., Vitale, I., Kepp, O., Kroemer, G. (eds) Cell Senescence. Methods in Molecular Biology, vol 965. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-239-1_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-239-1_23

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-238-4

  • Online ISBN: 978-1-62703-239-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation