Skip to main content
SpringerLink
Log in

HSP70 in Aging

  • Chapter
  • First Online:
Immunity, Tumors and Aging: The Role of HSP70

Part of the book series: SpringerBriefs in Biochemistry and Molecular Biology ((BRIEFSBIOCHEM,volume 6))

  • 990 Accesses

Abstract

Aging or senescence in biology is defined as the process of gradual loss of important body functions and cells, and in particular, the inability of cells to reproduce and cope with stress. Important features of an aging cell include the progressive accumulation of damaged proteins, abnormal protein aggregates and oxidative stress. Such features may damage macromolecules and trigger two genetic programs—cellular senescence and apoptosis. HSP70 limits cellular aging by: (i) ensuring the refolding and disaggregation of denatured/misfolded proteins; (ii) participating in the degradation of irreversibly dysfunctional proteins; (iii) mediating the effects of histone deacetylase 6 in the starvation-induced increase in life expectancy; and (iv) preventing cell senescence and apoptosis. However, cells of an aging body display a dramatic reduction of HSP70 inducibility. This reduction correlates with a decrease in the ability of cells to cope with stress. The reduction of HSP70 inducibility most likely reflects the launch of a special genetic program aimed at the activation of JNK-dependent apoptosis and the destruction of old cells, which have accumulated damaged proteins and dangerous mutations. Such a program functions to protect the body as a whole.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

References

  • Ambra R, Mocchegiani E, Giacconi R et al (2004) Characterization of the HSP70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation. Exp Gerontol 39(10):1475–1484

    Article  PubMed  CAS  Google Scholar 

  • Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 90:7915–7922

    Article  PubMed  CAS  Google Scholar 

  • Batulan Z, Shinder GA, Minotti S et al (2003) High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1. J Neurosci 23(13):5789–5798

    PubMed  CAS  Google Scholar 

  • Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581

    PubMed  CAS  Google Scholar 

  • Bellmann K, Jäättelä M, Wissing D, Burkart V, Kolb H (1996) Heat shock protein HSP70 overexpression confers resistance against nitric oxide. FEBS Lett 391(1–2):185–188

    Article  PubMed  CAS  Google Scholar 

  • Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272:20313–20316

    Article  PubMed  CAS  Google Scholar 

  • Bhat RV, Budd Haeberlein SL, Avila J (2004) Glycogen synthase kinase 3: a drug target for CNS therapies. J Neurochem 89(6):1313–1317

    Article  PubMed  CAS  Google Scholar 

  • Boyault C, Zhang Y, Fritah S et al (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 17:2172–2181

    Article  Google Scholar 

  • Corbi G, Conti V, Scapagnini G, Filippelli A, Ferrara N (2012) Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci (Elite Ed) 4:768–778

    Google Scholar 

  • Cortopassi GA, Wong A (1999) Mitochondria in organismal aging and degeneration. Biochim Biophys Acta 1410:183–193

    Article  PubMed  CAS  Google Scholar 

  • Cosulich S, Clarke P (1996) Apoptosis: does stress kill? Curr Biol 6(12):1586–1588

    Article  PubMed  CAS  Google Scholar 

  • Dall TM, Fulgoni VL 3rd, Zhang Y, Reimers KJ, Packard PT, Astwood JD (2009) Potential health benefits and medical cost savings from calorie, sodium, and saturated fat reductions in the American diet. Am J Health Promot 23(6):412–422

    Article  PubMed  Google Scholar 

  • Dice JF (2007) Chaperone-mediated autophagy. Autophagy 3(4):295–299

    PubMed  CAS  Google Scholar 

  • Everitt AV, Le Couteur DG (2007) Life extension by calorie restriction in humans. Ann N Y Acad Sci 1114:428–433

    Article  PubMed  Google Scholar 

  • Gabai VL, Kabakov AE (1993) Rise in heat-shock protein level confers tolerance to energy deprivation. FEBS Lett 327(3):247–250

    Article  PubMed  CAS  Google Scholar 

  • Gabai VL, Meriin AB, Mosser DD et al (1997) HSP70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance. J Biol Chem 272(29):18033–18037

    Article  PubMed  CAS  Google Scholar 

  • Gabai VL, Meriin AB, Yaglom JA, Volloch VZ, Sherman MY (1998) Role of HSP70 in regulation of stress-kinase JNK: implications in apoptosis and aging. FEBS Lett 438(1–2):1–4

    Article  PubMed  CAS  Google Scholar 

  • Gagliano N, Grizzi F, Annoni G (2007) Mechanisms of aging and liver functions. Dig Dis 25(2):118–123

    Article  PubMed  Google Scholar 

  • Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5(22):2592–2601

    Article  PubMed  CAS  Google Scholar 

  • Gutsmann-Conrad A, Heydari AR, You S, Richardson A (1998) The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res 241(2):404–413

    Article  PubMed  CAS  Google Scholar 

  • Hall DM, Oberley TD, Moseley PM et al (2000) Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats. FASEB J 14:78–86

    PubMed  CAS  Google Scholar 

  • Hands S, Sinadinos C, Wyttenbach A (2008) Polyglutamine gene function and dysfunction in the ageing brain. Biochim Biophys Acta 1779(8):507–521

    Article  PubMed  CAS  Google Scholar 

  • Heydari AR, Takahashi R, Gutsmann A, You S (1994) HSP70 and aging. Experientia 50(11–12):1092–1098

    Article  PubMed  CAS  Google Scholar 

  • Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300(5622):1142–1145

    Article  PubMed  CAS  Google Scholar 

  • Hut HM, Kampinga HH, Sibon OC (2005) HSP70 protects mitotic cells against heat-induced centrosome damage and division abnormalities. Mol Biol Cell 16(8):3776–3785

    Article  PubMed  CAS  Google Scholar 

  • Jäättelä M (1993) Overexpression of major heat shock protein HSP70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J Immunol 151(8):4286–4294

    PubMed  Google Scholar 

  • Jin X, Wang R, Xiao C et al (2004) Serum and lymphocyte levels of heat shock protein 70 in aging: a study in the normal Chinese population. Cell Stress Chaperones 9(1):69–75

    PubMed  CAS  Google Scholar 

  • Johnson FB, Sinclair DA, Guarente L (1999) Molecular biology of aging. Cell 2:291–302

    Article  Google Scholar 

  • Kayani AC, Morton JP, McArdle A (2008) The exercise-induced stress response in skeletal muscle: failure during aging. Appl Physiol Nutr Metab 33(5):1033–1041

    Article  PubMed  CAS  Google Scholar 

  • Kovacs JJ, Murphy PJ, Gaillard S et al (2005) HDAC6 regulates HSP90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18(5):601–607

    Article  PubMed  CAS  Google Scholar 

  • Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 92:2177–2186

    PubMed  CAS  Google Scholar 

  • Kregel KC, Moseley PL, Skidmore R, Gutierrez JA, Guerriero V (1995) HSP70 accumulation in tissues of heat-stressed rats is blunted with advancing age. J Appl Physiol 79:1673–1678

    PubMed  CAS  Google Scholar 

  • Li GC, Yang SH, Kim D et al (1995) Suppression of heat-induced HSP70 expression by the 70-kDa subunit of the human Ku autoantigen. Proc Natl Acad Sci U S A 92(10):4512–4516

    Article  PubMed  CAS  Google Scholar 

  • Lindquist S, Craig EA (1988) The heat-shock proteins. Annu Rev Genet 22:631–677

    Article  PubMed  CAS  Google Scholar 

  • Liu AY, Lee YK, Manalo D, Huang LE (1996) Attenuated heat shock transcriptional response in aging: molecular mechanism and implication in the biology of aging. EXS 77:393–408

    PubMed  CAS  Google Scholar 

  • Marques C, Guo W, Pereira P, Taylor A, Patterson C, Evans PC, Shang F (2006) The triage of damaged proteins: degradation by the ubiquitin-proteasome pathway or repair by molecular chaperones. FASEB J 20(6):741–743

    PubMed  CAS  Google Scholar 

  • Mayer MP, Bukau B (2005) HSP70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62(6):670–684

    Article  PubMed  CAS  Google Scholar 

  • McArdle A, Dillmann WH, Mestril R, Faulkner JA, Jackson MJ (2004) Overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction. FASEB J 18:355–357

    PubMed  CAS  Google Scholar 

  • Mignotte B, Vayssiere JL (1998) Mitochondria and apoptosis. Eur J Biochem 252(1):1–15

    Article  PubMed  CAS  Google Scholar 

  • Min JN, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C (2008) CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol 28(12):4018–4025

    Article  PubMed  CAS  Google Scholar 

  • Minois N, Khazaeli AA, Curtsinger JW (2001) Locomotor activity as a function of age and life span in Drosophila melanogaster overexpressing HSP70. Exp Gerontol 36(7):1137–1153

    Article  PubMed  CAS  Google Scholar 

  • Mosser DD, Martin LH (1992) Induced thermotolerance to apoptosis in a human T lymphocyte cell line. J Cell Physiol 151(3):561–570

    Article  PubMed  CAS  Google Scholar 

  • Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B (1997) Role of the human heat shock protein HSP70 in protection against stress-induced apoptosis. Mol Cell Biol 17(9):5317–5327

    PubMed  CAS  Google Scholar 

  • Njemini R, Abeele MV, Demanet C, Lambert M, Vandebosch S, Mets T (2002) Age-related decrease in the inducibility of heat-shock protein 70 in human peripheral blood mononuclear cells. J Clin Immunol 22(4):195–205

    Article  PubMed  CAS  Google Scholar 

  • Papaconstantinou J (1994) Unifying model of the programmed (intrinsic) and stochastic (extrinsic) theories of aging. Ann NY Acad Sci 719:195–211

    Article  PubMed  CAS  Google Scholar 

  • Powis G, Briehl M, Oblong J (1995) Redox signalling and the control of cell growth and death. Pharmacol Ther 68:149–173

    Article  PubMed  CAS  Google Scholar 

  • Raffray M, Cohen GM (1997) Apoptosis and necrosis in toxicology: a continuum or distinct modes of cell death? Pharmacol Ther 75(3):153–177

    Article  PubMed  CAS  Google Scholar 

  • Rujano MA, Bosveld F, Salomons FA et al. (2006) Polarised asymmetric inheritance of accumulated protein damage in higher eukaryotes. PLoS Biol 4(12):e417

    Google Scholar 

  • Salvesen GS, Dixit VM (1997) Caspases: intracellular signaling by proteolysis. Cell 91(4):443–446

    Article  PubMed  CAS  Google Scholar 

  • Seimiya H, Mashima T, Toho M, Tsuruo T (1997) c-Jun NH2-terminal kinase-mediated activation of interleukin-1beta converting enzyme/CED-3-like protease during anticancer drug-induced apoptosis. J Biol Chem 272(7):4631–4636

    Article  PubMed  CAS  Google Scholar 

  • Sherman MY, Goldberg AL (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29(1):15–32

    Article  PubMed  CAS  Google Scholar 

  • Sherman H, Frumin I, Gutman R, Chapnik N, Lorentz A, Meylan J, le Coutre J, Froy O (2011) Long-term restricted feeding alters circadian expression and reduces the level of inflammatory and disease markers. J Cell Mol Med 15(12):2745–2759

    Article  PubMed  CAS  Google Scholar 

  • Simon MM, Reikerstorfer A, Schwarz A et al (1995) Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release. J Clin Invest 95(3):926–933

    Article  PubMed  CAS  Google Scholar 

  • Singh R, Kølvraa S, Bross P et al (2006) Reduced heat shock response in human mononuclear cells during aging and its association with polymorphisms in HSP70 genes. Cell Stress Chaperones 11(3):208–215

    Article  PubMed  CAS  Google Scholar 

  • Singh R, Kolvraa S, Rattan SI (2007) Genetics of human longevity with emphasis on the relevance of HSP70 as candidate genes. Front Biosci 12:4504–4513

    Article  PubMed  CAS  Google Scholar 

  • Steinkraus KA, Smith ED, Davis C et al (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7(3):394–404

    Article  PubMed  CAS  Google Scholar 

  • Verheij M, Bose R, Lin XH, Yao B et al (1996) Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380(6569):75–79

    Article  PubMed  CAS  Google Scholar 

  • Visala Rao D, Boyle GM, Parsons PG, Watson K, Jones GL (2003) Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes. Mech Ageing Dev 124(1):55–69

    Article  PubMed  CAS  Google Scholar 

  • Volloch V, Mosser DD, Massie B, Sherman MY (1998) Reduced thermotolerance in aged cells results from a loss of an HSP72-mediated control of JNK signaling pathway. Cell Stress Chaperones 3(4):265–271

    PubMed  CAS  Google Scholar 

  • Webb SJ, Harrison DJ, Wyllie AH (1997) Apoptosis: an overview of the process and its relevance in disease. Adv Pharmacol 41:1–34

    Article  PubMed  CAS  Google Scholar 

  • Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI (2009) Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323(5917):1063–1066

    Article  PubMed  CAS  Google Scholar 

  • Westphal CH, Dipp MA, Guarente L (2007) A therapeutic role for sirtuins in diseases of aging? Trends Biochem Sci 32(12):555–560

    Article  PubMed  CAS  Google Scholar 

  • Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J 27(2):336–349

    Article  PubMed  CAS  Google Scholar 

  • Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270(5240):1326–1331

    Article  PubMed  CAS  Google Scholar 

  • Zanke BW, Boudreau K, Rubie E et al (1996) The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr Biol 6(5):606–613

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Moscow State University of Medicine and Dentistry, St 20/1 Delegatskaya, Moscow, Russia, 127473

    Igor Malyshev

Authors
  1. Igor Malyshev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Igor Malyshev .

Rights and permissions

Reprints and permissions

Copyright information

© 2013 The Author(s)

About this chapter

Cite this chapter

Malyshev, I. (2013). HSP70 in Aging. In: Immunity, Tumors and Aging: The Role of HSP70. SpringerBriefs in Biochemistry and Molecular Biology, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5943-5_7

Download citation

Publish with us

Policies and ethics

Search

Navigation