Abstract
The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Kourtis N, Tavernarakis N (2011) Cellular stress response pathways and ageing: intricate molecular relationships. EMBO J 30:2520–2531
Salminen A, Kaarniranta K (2010) ER stress and hormetic regulation of the aging process. Ageing Res Rev 9:211–217
Tower J (2009) Hsps and aging. Trends Endocrinol Metab 20:216–222
Balch WE, Morimoto RI, Dillin A, Kelly JW (2008) Adapting proteostasis for disease intervention. Science 319:916–919
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217
Haynes CM, Ron D (2010) The mitochondrial UPR—protecting organelle protein homeostasis. J Cell Sci 123:3849–3855
Bartoszewska M, Williams C, Kikhney A, Opalinski L, van Roermund CW, de Boer R, Veenhuis M, van der Klei IJ (2012) Peroxisomal proteostasis involves a Lon family protein that functions as protease and chaperone. J Biol Chem 287:27380–27395
Morimoto RI (2011) The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol 76:91–99
Koga H, Kaushik S, Cuervo AM (2011) Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res Rev 10:205–215
Akerfelt M, Morimoto RI, Sistonen L (2010) Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol 11:545–555
Wu C (1995) Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol 11:441–469
Bu L, Jin Y, Shi Y, Chu R, Ban A, Eiberg H, Andres L, Jiang H, Zheng G, Qian M, Cui B, Xia Y, Liu J, Hu L, Zhao G, Hayden MR, Kong X (2002) Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract. Nat Genet 31:276–278
Fujimoto M, Izu H, Seki K, Fukuda K, Nishida T, Yamada S, Kato K, Yonemura S, Inouye S, Nakai A (2004) HSF4 is required for normal cell growth and differentiation during mouse lens development. EMBO J 23:4297–4306
Kallio M, Chang Y, Manuel M, Alastalo TP, Rallu M, Gitton Y, Pirkkala L, Loones MT, Paslaru L, Larney S, Hiard S, Morange M, Sistonen L, Mezger V (2002) Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice. EMBO J 21:2591–2601
Morimoto RI (2008) Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev 22:1427–1438
Sistonen L, Sarge KD, Phillips B, Abravaya K, Morimoto RI (1992) Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells. Mol Cell Biol 12:4104–4111
Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R (1998) Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94:471–480
Sorger PK, Nelson HC (1989) Trimerization of a yeast transcriptional activator via a coiled-coil motif. Cell 59:807–813
Cotto J, Fox S, Morimoto R (1997) HSF1 granules: a novel stress-induced nuclear compartment of human cells. J Cell Sci 110(Pt 23):2925–2934
Guettouche T, Boellmann F, Lane WS, Voellmy R (2005) Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress. BMC Biochem 6:4
Holmberg CI, Hietakangas V, Mikhailov A, Rantanen JO, Kallio M, Meinander A, Hellman J, Morrice N, MacKintosh C, Morimoto RI, Eriksson JE, Sistonen L (2001) Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J 20:3800–3810
Kline MP, Morimoto RI (1997) Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol 17:2107–2115
Knauf U, Newton EM, Kyriakis J, Kingston RE (1996) Repression of human heat shock factor 1 activity at control temperature by phosphorylation. Genes Dev 10:2782–2793
Sorger PK, Pelham HR (1988) Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell 54:855–864
Anckar J, Hietakangas V, Denessiouk K, Thiele DJ, Johnson MS, Sistonen L (2006) Inhibition of DNA binding by differential sumoylation of heat shock factors. Mol Cell Biol 26:955–964
Hietakangas V, Ahlskog JK, Jakobsson AM, Hellesuo M, Sahlberg NM, Holmberg CI, Mikhailov A, Palvimo JJ, Pirkkala L, Sistonen L (2003) Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Mol Cell Biol 23:2953–2968
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 323:1063–1066
Raynes R, Leckey BD Jr, Nguyen K, Westerheide SD (2012) Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. J Biol Chem 287:29045–29053
Shi Y, Mosser DD, Morimoto RI (1998) Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev 12:654–666
Raynes R, Pombier KM, Nguyen K, Brunquell J, Mendez JE, Westerheide SD (2013) The SIRT1 modulators AROS and DBC1 regulate HSF1 activity and the heat shock response. PLoS One 8:e54364
Ben-Zvi A, Miller EA, Morimoto RI (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci U S A 106:14914–14919
Shemesh N, Shai N, Ben-Zvi A (2013) Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood. Aging Cell 12:814–822
Angeli S, Klang I, Sivapatham R, Mark K, Zucker D, Bhaumik D, Lithgow GJ, Andersen JK (2013) A DNA synthesis inhibitor is protective against proteotoxic stressors via modulation of fertility pathways in Caenorhabditis elegans. Aging (Albany NY) 5:759–769
Morrow G, Samson M, Michaud S, Tanguay RM (2004) Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J 18:598–599
Walker GA, Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2:131–139
Swindell WR, Masternak MM, Kopchick JJ, Conover CA, Bartke A, Miller RA (2009) Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice. Mech Ageing Dev 130:393–400
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 28:4018–4025
Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145
Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15:657–664
Chiang WC, Ching TT, Lee HC, Mousigian C, Hsu AL (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148:322–334
Maman M, Carvalhal Marques F, Volovik Y, Dubnikov T, Bejerano-Sagie M, Cohen E (2013) A neuronal GPCR is critical for the induction of the heat shock response in the nematode C. elegans. J Neurosci 33:6102–6111
Shinkawa T, Tan K, Fujimoto M, Hayashida N, Yamamoto K, Takaki E, Takii R, Prakasam R, Inouye S, Mezger V, Nakai A (2011) Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation. Mol Biol Cell 22:3571–3583
Marcuccilli CJ, Mathur SK, Morimoto RI, Miller RJ (1996) Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock. J Neurosci 16:478–485
Vihervaara A, Sergelius C, Vasara J, Blom MA, Elsing AN, Roos-Mattjus P, Sistonen L (2013) Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells. Proc Natl Acad Sci U S A 110:E3388–E3397
Gandhapudi SK, Murapa P, Threlkeld ZD, Ward M, Sarge KD, Snow C, Woodward JG (2013) Heat shock transcription factor 1 is activated as a consequence of lymphocyte activation and regulates a major proteostasis network in T cells critical for cell division during stress. J Immunol 191:4068–4079
Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115
Shamovsky I, Ivannikov M, Kandel ES, Gershon D, Nudler E (2006) RNA-mediated response to heat shock in mammalian cells. Nature 440:556–560
Kugel JF, Goodrich JA (2006) Beating the heat: a translation factor and an RNA mobilize the heat shock transcription factor HSF1. Mol Cell 22:153–154
Ahn SG, Thiele DJ (2003) Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev 17:516–528
Lu M, Lee YJ, Park SM, Kang HS, Kang SW, Kim S, Park JS (2009) Aromatic-participant interactions are essential for disulfide-bond-based trimerization in human heat shock transcription factor 1. Biochemistry 48:3795–3797
Prahlad V, Cornelius T, Morimoto RI (2008) Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons. Science 320:811–814
Gallo GJ, Prentice H, Kingston RE (1993) Heat shock factor is required for growth at normal temperatures in the fission yeast Schizosaccharomyces pombe. Mol Cell Biol 13:749–761
Jedlicka P, Mortin MA, Wu C (1997) Multiple functions of Drosophila heat shock transcription factor in vivo. EMBO J 16:2452–2462
Christians E, Davis AA, Thomas SD, Benjamin IJ (2000) Maternal effect of Hsf1 on reproductive success. Nature 407:693–694
Inouye S, Izu H, Takaki E, Suzuki H, Shirai M, Yokota Y, Ichikawa H, Fujimoto M, Nakai A (2004) Impaired IgG production in mice deficient for heat shock transcription factor 1. J Biol Chem 279:38701–38709
Takii R, Inouye S, Fujimoto M, Nakamura T, Shinkawa T, Prakasam R, Tan K, Hayashida N, Ichikawa H, Hai T, Nakai A (2010) Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3. J Immunol 184:1041–1048
Barna J, Princz A, Kosztelnik M, Hargitai B, Takacs-Vellai K, Vellai T (2012) Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to control development and aging. BMC Dev Biol 12:32
Dai C, Whitesell L, Rogers AB, Lindquist S (2007) Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130:1005–1018
Min JN, Huang L, Zimonjic DB, Moskophidis D, Mivechi NF (2007) Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors. Oncogene 26:5086–5097
Kim EH, Lee YJ, Bae S, Lee JS, Kim J, Lee YS (2009) Heat shock factor 1-mediated aneuploidy requires a defective function of p53. Cancer Res 69:9404–9412
Whitesell L, Lindquist S (2009) Inhibiting the transcription factor HSF1 as an anticancer strategy. Expert Opin Ther Targets 13:469–478
Travers KJ, Patil CK, Wodicka L, Lockhart DJ, Weissman JS, Walter P (2000) Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101:249–258
Schroder M (2008) Endoplasmic reticulum stress responses. Cell Mol Life Sci 65:862–894
Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9:2277–2293
Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8:519–529
Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (2000) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 5:897–904
Chen X, Shen J, Prywes R (2002) The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J Biol Chem 277:13045–13052
Shen J, Chen X, Hendershot L, Prywes R (2002) ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3:99–111
Han D, Lerner AG, Vande Walle L, Upton JP, Xu W, Hagen A, Backes BJ, Oakes SA, Papa FR (2009) IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138:562–575
Szegezdi E, Logue SE, Gorman AM, Samali A (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:880–885
Fribley A, Zhang K, Kaufman RJ (2009) Regulation of apoptosis by the unfolded protein response. Methods Mol Biol 559:191–204
Samali A, Fitzgerald U, Deegan S, Gupta S (2010) Methods for monitoring endoplasmic reticulum stress and the unfolded protein response. Int J Cell Biol 2010:830307
Iwawaki T, Akai R, Kohno K, Miura M (2004) A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat Med 10:98–102
Merksamer PI, Trusina A, Papa FR (2008) Real-time redox measurements during endoplasmic reticulum stress reveal interlinked protein folding functions. Cell 135:933–947
Thorp E, Iwawaki T, Miura M, Tabas I (2011) A reporter for tracking the UPR in vivo reveals patterns of temporal and cellular stress during atherosclerotic progression. J Lipid Res 52:1033–1038
Hiramatsu N, Kasai A, Hayakawa K, Yao J, Kitamura M (2006) Real-time detection and continuous monitoring of ER stress in vitro and in vivo by ES-TRAP: evidence for systemic, transient ER stress during endotoxemia. Nucleic Acids Res 34:e93
Chitnis N, Pytel D, Diehl JA (2013) UPR-inducible miRNAs contribute to stressful situations. Trends Biochem Sci 38:447–452
Bartoszewska S, Kochan K, Madanecki P, Piotrowski A, Ochocka R, Collawn JF, Bartoszewski R (2013) Regulation of the unfolded protein response by microRNAs. Cell Mol Biol Lett 18(4):555–578
Chitnis NS, Pytel D, Bobrovnikova-Marjon E, Pant D, Zheng H, Maas NL, Frederick B, Kushner JA, Chodosh LA, Koumenis C, Fuchs SY, Diehl JA (2012) miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner. Mol Cell 48:353–364
Byrd AE, Aragon IV, Brewer JW (2012) MicroRNA-30c-2* limits expression of proadaptive factor XBP1 in the unfolded protein response. J Cell Biol 196:689–698
Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA (2012) IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 338:818–822
Cawley K, Logue SE, Gorman AM, Zeng Q, Patterson J, Gupta S, Samali A (2013) Disruption of microRNA biogenesis confers resistance to ER stress-induced cell death upstream of the mitochondrion. PLoS One 8:e73870
Naidoo N, Ferber M, Master M, Zhu Y, Pack AI (2008) Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. J Neurosci 28:6539–6548
Hussain SG, Ramaiah KV (2007) Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochem Biophys Res Commun 355:365–370
Nuss JE, Choksi KB, DeFord JH, Papaconstantinou J (2008) Decreased enzyme activities of chaperones PDI and BiP in aged mouse livers. Biochem Biophys Res Commun 365:355–361
Paz Gavilan M, Vela J, Castano A, Ramos B, del Rio JC, Vitorica J, Ruano D (2006) Cellular environment facilitates protein accumulation in aged rat hippocampus. Neurobiol Aging 27:973–982
Engin F, Yermalovich A, Ngyuen T, Hummasti S, Fu W, Eizirik DL, Mathis D, Hotamisligil GS (2013) Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. Sci Transl Med 5: 211ra156
Haskins KA, Russell JF, Gaddis N, Dressman HK, Aballay A (2008) Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell 15:87–97
Sun J, Singh V, Kajino-Sakamoto R, Aballay A (2011) Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332:729–732
Menu P, Mayor A, Zhou R, Tardivel A, Ichijo H, Mori K, Tschopp J (2012) ER stress activates the NLRP3 inflammasome via an UPR-independent pathway. Cell Death Dis 3:e261
Lu M, Sun XL, Qiao C, Liu Y, Ding JH, Hu G (2014) Uncoupling protein 2 deficiency aggravates astrocytic endoplasmic reticulum stress and nod-like receptor protein 3 inflammasome activation. Neurobiol Aging 35:421–430
Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, Shen S, Nguyen V, Backes BJ, Heiman M, Heintz N, Greengard P, Hui S, Tang Q, Trusina A, Oakes SA, Papa FR (2012) IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 16:250–264
Oslowski CM, Hara T, O’Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, Greiner D, Kaufman RJ, Bortell R, Urano F (2012) Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome. Cell Metab 16:265–273
Bishop NA, Guarente L (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–549
Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci U S A 102:3105–3110
Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–366
Ermolaeva MA, Segref A, Dakhovnik A, Ou HL, Schneider JI, Utermohlen O, Hoppe T, Schumacher B (2013) DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature 501:416–420
Lionaki E, Tavernarakis N (2013) Oxidative stress and mitochondrial protein quality control in aging. J Proteome 92:181–194
Raffaello A, Rizzuto R (2011) Mitochondrial longevity pathways. Biochim Biophys Acta 1813:260–268
Durieux J, Wolff S, Dillin A (2011) The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell 144:79–91
Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153:1435–1447
Sun J, Liu Y, Aballay A (2012) Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation. EMBO Rep 13:855–860
Guisbert E, Czyz DM, Richter K, McMullen PD, Morimoto RI (2013) Identification of a tissue-selective heat shock response regulatory network. PLoS Genet 9:e1003466
van Oosten-Hawle P, Porter RS, Morimoto RI (2013) Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153:1366–1378
Prahlad V, Morimoto RI (2011) Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins. Proc Natl Acad Sci U S A 108:14204–14209
Schneeberger M, Dietrich MO, Sebastian D, Imbernon M, Castano C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodriguez IC, Bortolozzi A, Garcia-Roves PM, Gomis R, Nogueiras R, Horvath TL, Zorzano A, Claret M (2013) Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155:172–187
Ben-Gedalya T, Cohen E (2012) Quality control compartments coming of age. Traffic 13:635–642
Kregel KC (2002) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol (1985) 92:2177–2186
Fargnoli J, Kunisada T, Fornace AJ Jr, Schneider EL, Holbrook NJ (1990) Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc Natl Acad Sci U S A 87:846–850
Liu AY, Lin Z, Choi HS, Sorhage F, Li B (1989) Attenuated induction of heat shock gene expression in aging diploid fibroblasts. J Biol Chem 264:12037–12045
Blake MJ, Fargnoli J, Gershon D, Holbrook NJ (1991) Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats. Am J Physiol 260:R663–R667
Hall DM, Xu L, Drake VJ, Oberley LW, Oberley TD, Moseley PL, Kregel KC (2000) Aging reduces adaptive capacity and stress protein expression in the liver after heat stress. J Appl Physiol (1985) 89:749–759
Kregel KC, Moseley PL, Skidmore R, Gutierrez JA, Guerriero V Jr (1995) HSP70 accumulation in tissues of heat-stressed rats is blunted with advancing age. J Appl Physiol (1985) 79:1673–1678
Nitta Y, Abe K, Aoki M, Ohno I, Isoyama S (1994) Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia. Am J Physiol 267:H1795–H1803
Fawcett TW, Sylvester SL, Sarge KD, Morimoto RI, Holbrook NJ (1994) Effects of neurohormonal stress and aging on the activation of mammalian heat shock factor 1. J Biol Chem 269:32272–32278
Locke M, Tanguay RM (1996) Diminished heat shock response in the aged myocardium. Cell Stress Chaperones 1:251–260
Hageman J, Rujano MA, van Waarde MA, Kakkar V, Dirks RP, Govorukhina N, Oosterveld-Hut HM, Lubsen NH, Kampinga HH (2010) A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol Cell 37:355–369
Kazemi-Esfarjani P, Benzer S (2000) Genetic suppression of polyglutamine toxicity in Drosophila. Science 287:1837–1840
Labbadia J, Novoselov SS, Bett JS, Weiss A, Paganetti P, Bates GP, Cheetham ME (2012) Suppression of protein aggregation by chaperone modification of high molecular weight complexes. Brain 135:1180–1196
Chafekar SM, Duennwald ML (2012) Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin. PLoS One 7:e37929
Riva L, Koeva M, Yildirim F, Pirhaji L, Dinesh D, Mazor T, Duennwald ML, Fraenkel E (2012) Poly-glutamine expanded huntingtin dramatically alters the genome wide binding of HSF1. J Huntingtons Dis 1:33–45
Wang AM, Miyata Y, Klinedinst S, Peng HM, Chua JP, Komiyama T, Li X, Morishima Y, Merry DE, Pratt WB, Osawa Y, Collins CA, Gestwicki JE, Lieberman AP (2013) Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol 9:112–118
Calamini B, Silva MC, Madoux F, Hutt DM, Khanna S, Chalfant MA, Allais C, Ouizem S, Saldanha SA, Ferguson J, Mercer BA, Michael C, Tait BD, Garza D, Balch WE, Roush WR, Morimoto RI, Hodder P (2010) ML346: a novel modulator of proteostasis for protein conformational diseases. In: Probe reports from the NIH Molecular Libraries Program. National Center for Biotechnology Information (US), Bethesda, MD
Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454:455–462
Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917
Harding HP, Zeng H, Zhang Y, Jungries R, Chung P, Plesken H, Sabatini DD, Ron D (2001) Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival. Mol Cell 7:1153–1163
Back SH, Scheuner D, Han J, Song B, Ribick M, Wang J, Gildersleeve RD, Pennathur S, Kaufman RJ (2009) Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells. Cell Metab 10:13–26
Alavez S, Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ (2011) Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472:226–229
Schulze A, Harris AL (2012) How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 491:364–373
Koong AC, Chauhan V, Romero-Ramirez L (2006) Targeting XBP-1 as a novel anti-cancer strategy. Cancer Biol Ther 5:756–759
Ryno LM, Wiseman RL, Kelly JW (2013) Targeting unfolded protein response signaling pathways to ameliorate protein misfolding diseases. Curr Opin Chem Biol 17:346–352
Calamini B, Silva MC, Madoux F, Hutt DM, Khanna S, Chalfant MA, Saldanha SA, Hodder P, Tait BD, Garza D, Balch WE, Morimoto RI (2012) Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol 8:185–196
Pyrko P, Schonthal AH, Hofman FM, Chen TC, Lee AS (2007) The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer Res 67:9809–9816
Buontempo F, Orsini E, Martins LR, Antunes I, Lonetti A, Chiarini F, Tabellini G, Evangelisti C, Melchionda F, Pession A, Bertaina A, Locatelli F, McCubrey JA, Cappellini A, Barata JT, Martelli AM (2013) Cytotoxic activity of the casein kinase 2 inhibitor CX-4945 against T-cell acute lymphoblastic leukemia: targeting the unfolded protein response signaling. Leukemia 28(3):543–553
Vilchez D, Boyer L, Morantte I, Lutz M, Merkwirth C, Joyce D, Spencer B, Page L, Masliah E, Berggren WT, Gage FH, Dillin A (2012) Increased proteasome activity in human embryonic stem cells is regulated by PSMD11. Nature 489:304–308
Chung CY, Khurana V, Auluck PK, Tardiff DF, Mazzulli JR, Soldner F, Baru V, Lou Y, Freyzon Y, Cho S, Mungenast AE, Muffat J, Mitalipova M, Pluth MD, Jui NT, Schule B, Lippard SJ, Tsai LH, Krainc D, Buchwald SL, Jaenisch R, Lindquist S (2013) Identification and rescue of alpha-synuclein toxicity in Parkinson patient-derived neurons. Science 342:983–987
Heijmans J, Lidth v, de Jeude JF, Koo BK, Rosekrans SL, Wielenga MC, van de Wetering M, Ferrante M, Lee AS, Onderwater JJ, Paton JC, Paton AW, Mommaas AM, Kodach LL, Hardwick JC, Hommes DW, Clevers H, Muncan V, van den Brink GR (2013) ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep 3:1128–1139
Rouault-Pierre K, Lopez-Onieva L, Foster K, Anjos-Afonso F, Lamrissi-Garcia I, Serrano-Sanchez M, Mitter R, Ivanovic Z, de Verneuil H, Gribben J, Taussig D, Rezvani HR, Mazurier F, Bonnet D (2013) HIF-2alpha protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stress. Cell Stem Cell 13:549–563
Acknowledgements
We apologize to those colleagues whose work could not be referenced directly owing to space limitations. E.K. is supported by the General Secretariat for Research and Technology of the Greek Ministry of Education. A.P. is supported by a European Commission Marie Curie Actions Programme, Initial Training fellowship. Work in the authors’ laboratory is also funded by grants from the European Research Council (ERC) and the European Commission Seventh Framework Programme.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Kyriakakis, E., Princz, A., Tavernarakis, N. (2015). Stress Responses During Ageing: Molecular Pathways Regulating Protein Homeostasis. In: Oslowski, C. (eds) Stress Responses. Methods in Molecular Biology, vol 1292. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2522-3_16
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2522-3_16
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2521-6
Online ISBN: 978-1-4939-2522-3
eBook Packages: Springer Protocols