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Annual Review of Pathology: Mechanisms of Disease

Volume 10, 2015

The Roles of Cellular and Organismal Aging in the Development of Late-Onset Maladies

Abstract

Numerous disorders, including neurodegenerative diseases and certain types of cancer, manifest late in life. This common feature raises the prospect that an aging-associated decline in the activity of cellular and organismal maintenance mechanisms enables the emergence of these maladies in late life stages. Accordingly, the alteration of aging bears the promise of harnessing the mechanisms that protect the young organism to prevent illness in the elderly. The identification of aging-regulatory pathways has enabled scrutiny of this hypothesis and revealed that the alteration of aging protects invertebrates and mammals from toxic protein aggregation linked to neurodegeneration and from cancer. Here we review the current knowledge on the regulation of aging at the cellular and organismal levels, delineate the mechanistic links between aging and late-onset disorders, describe efforts to develop compounds that protect from these maladies by selectively manipulating aging, and discuss future research directions and possible therapeutic implications of this approach.

Keyword(s): dietary restriction, insulin/IGF-1 signaling, neurodegeneration, proteostasis, proteotoxicity, stress resistance
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/content/journals/10.1146/annurev-pathol-012414-040508
2015-01-24
2024-04-18
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Literature Cited

  1. Rose M, Charlesworth B. 1.  1980. A test of evolutionary theories of senescence. Nature 287:141–42 [Google Scholar]
  2. Harman D. 2.  1956. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11:298–300 [Google Scholar]
  3. Harman D. 3.  1972. The biologic clock: the mitochondria?. J. Am. Geriatr. Soc. 20:145–47 [Google Scholar]
  4. Reichel W. 4.  1966. The biology of aging. J. Am. Geriatr. Soc. 14:431–36 [Google Scholar]
  5. Weismann A. 5.  1889. Essays upon Heredity and Kindred Biological Problems Oxford, UK: Clarendon
  6. Hjelmborg JvB, Iachine I, Skytthe A, Vaupel JW, McGue M. 6.  et al. 2006. Genetic influence on human lifespan and longevity. Hum. Genet. 119:312–21 [Google Scholar]
  7. Mair W, Dillin A. 7.  2008. Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77:727–54 [Google Scholar]
  8. Kenyon CJ. 8.  2010. The genetics of ageing. Nature 464:504–12 [Google Scholar]
  9. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW. 9.  et al. 2010. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 11:453–65 [Google Scholar]
  10. Wolff S, Dillin A. 10.  2006. The trifecta of aging in Caenorhabditis elegans. Exp. Gerontol. 41:894–903 [Google Scholar]
  11. McCay CM, Crowell MF, Maynard LA. 11.  1989. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 5:155–71; discussion 172 [Google Scholar]
  12. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ. 12.  et al. 2009. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–4 [Google Scholar]
  13. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM. 13.  et al. 2012. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489:318–21 [Google Scholar]
  14. Panowski SH, Wolff S, Aguilaniu H, Durieux J, Dillin A. 14.  2007. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature 447:550–55 [Google Scholar]
  15. Bishop NA, Guarente L. 15.  2007. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–49Reports that SKN-1/Nrf activity in ASI neurons is crucial for DR-mediated longevity. [Google Scholar]
  16. Carrano AC, Liu Z, Dillin A, Hunter T. 16.  2009. A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature 460:396–99 [Google Scholar]
  17. Park SK, Link CD, Johnson TE. 17.  2010. Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24:383–92 [Google Scholar]
  18. Vora M, Shah M, Ostafi S, Onken B, Xue J. 18.  et al. 2013. Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan. PLOS Genet. 9:e1003737 [Google Scholar]
  19. Friedman DB, Johnson TE. 19.  1988. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118:75–86 [Google Scholar]
  20. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R. 20.  1993. A C. elegans mutant that lives twice as long as wild type. Nature 366:461–64 [Google Scholar]
  21. Chen Z, Hendricks M, Cornils A, Maier W, Alcedo J, Zhang Y. 21.  2013. Two insulin-like peptides antagonistically regulate aversive olfactory learning in C. elegans. Neuron 77:572–85 [Google Scholar]
  22. Li W, Kennedy SG, Ruvkun G. 22.  2003. daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev. 17:844–58 [Google Scholar]
  23. Morris JZ, Tissenbaum HA, Ruvkun G. 23.  1996. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536–39 [Google Scholar]
  24. Ogg S, Ruvkun G. 24.  1998. The C. elegans PTEN homolog, DAF-18, acts in the insulin receptor–like metabolic signaling pathway. Mol. Cell 2:887–93 [Google Scholar]
  25. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM. 25.  1999. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398:630–34 [Google Scholar]
  26. Paradis S, Ruvkun G. 26.  1998. Caenorhabditis elegans Akt/PKB transduces insulin receptor–like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev. 12:2488–98 [Google Scholar]
  27. Henderson ST, Johnson TE. 27.  2001. daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr. Biol. 11:1975–80 [Google Scholar]
  28. Lee RY, Hench J, Ruvkun G. 28.  2001. Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr. Biol. 11:1950–57 [Google Scholar]
  29. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY. 29.  et al. 2008. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132:1025–38Reveals that SKN-1/Nrf is regulated by the IIS cascade, linking this pathway to DR. [Google Scholar]
  30. Chiang WC, Ching TT, Lee HC, Mousigian C, Hsu AL. 30.  2012. HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148:322–34Shows that the IIS pathway directly regulates the activity of HSF-1. [Google Scholar]
  31. Tepper RG, Ashraf J, Kaletsky R, Kleemann G, Murphy CT, Bussemaker HJ. 31.  2013. PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity. Cell 154:676–90 [Google Scholar]
  32. Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A. 32.  2006. SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124:1039–53 [Google Scholar]
  33. Riedel CG, Dowen RH, Lourenco GF, Kirienko NV, Heimbucher T. 33.  et al. 2013. DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nat. Cell Biol. 15:491–501 [Google Scholar]
  34. Ayyadevara S, Alla R, Thaden JJ, Shmookler Reis RJ. 34.  2008. Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell 7:13–22 [Google Scholar]
  35. Giannakou ME, Goss M, Jacobson J, Vinti G, Leevers SJ, Partridge L. 35.  2007. Dynamics of the action of dFOXO on adult mortality in Drosophila. Aging Cell 6:429–38 [Google Scholar]
  36. Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A. 36.  et al. 2003. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–87Indicates that the aging-regulatory mechanism downstream of the IIS cascade is conserved in mammals. [Google Scholar]
  37. Anselmi CV, Malovini A, Roncarati R, Novelli V, Villa F. 37.  et al. 2009. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 12:95–104 [Google Scholar]
  38. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H. 38.  et al. 2009. Association of FOXO3A variation with human longevity confirmed in German centenarians. PNAS 106:2700–5 [Google Scholar]
  39. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B. 39.  et al. 2008. Functionally significant insulin-like growth factor I receptor mutations in centenarians. PNAS 105:3438–42 [Google Scholar]
  40. Willcox BJ, Donlon TA, He Q, Chen R, Grove JS. 40.  et al. 2008. FOXO3A genotype is strongly associated with human longevity. PNAS 105:13987–92 [Google Scholar]
  41. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Müller F. 41.  2003. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620 [Google Scholar]
  42. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. 42.  2004. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14:885–90 [Google Scholar]
  43. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM. 43.  et al. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–95 [Google Scholar]
  44. Ma XM, Blenis J. 44.  2009. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10:307–18 [Google Scholar]
  45. Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C. 45.  2007. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6:95–110 [Google Scholar]
  46. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ. 46.  et al. 2009. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326:140–44 [Google Scholar]
  47. Finkel T, Deng CX, Mostoslavsky R. 47.  2009. Recent progress in the biology and physiology of sirtuins. Nature 460:587–91 [Google Scholar]
  48. Tissenbaum HA, Guarente L. 48.  2001. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–30 [Google Scholar]
  49. Rogina B, Helfand SL. 49.  2004. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. PNAS 101:15998–6003 [Google Scholar]
  50. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvari M. 50.  et al. 2011. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477:482–85 [Google Scholar]
  51. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G. 51.  et al. 2012. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483:218–21 [Google Scholar]
  52. Hsin H, Kenyon C. 52.  1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–66 [Google Scholar]
  53. Mukhopadhyay A, Tissenbaum HA. 53.  2007. Reproduction and longevity: secrets revealed by C. elegans. Trends Cell Biol. 17:65–71 [Google Scholar]
  54. Flatt T, Min KJ, D'Alterio C, Villa-Cuesta E, Cumbers J. 54.  et al. 2008. Drosophila germ-line modulation of insulin signaling and lifespan. PNAS 105:6368–73 [Google Scholar]
  55. Cargill SL, Carey JR, Müller HG, Anderson G. 55.  2003. Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2:185–90 [Google Scholar]
  56. Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H. 56.  et al. 2002. Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–401 [Google Scholar]
  57. Feng J, Bussiere F, Hekimi S. 57.  2001. Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev. Cell 1:633–44 [Google Scholar]
  58. Lakowski B, Hekimi S. 58.  1996. Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272:1010–13 [Google Scholar]
  59. Takahashi K, Noda Y, Ohsawa I, Shirasawa T, Takahashi M. 59.  2014. Extended lifespan, reduced body size and leg skeletal muscle mass, and decreased mitochondrial function in clk-1 transgenic mice. Exp. Gerontol. 58:146–53 [Google Scholar]
  60. Sheaffer KL, Updike DL, Mango SE. 60.  2008. The target of rapamycin pathway antagonizes pha-4/FoxA to control development and aging. Curr. Biol. 18:1355–64 [Google Scholar]
  61. Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD. 61.  et al. 2012. TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 15:713–24 [Google Scholar]
  62. Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ. 62.  2013. Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell 12:1073–81 [Google Scholar]
  63. Chen D, Thomas EL, Kapahi P. 63.  2009. HIF-1 modulates dietary restriction–mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLOS Genet. 5:e1000486 [Google Scholar]
  64. Lee SJ, Hwang AB, Kenyon C. 64.  2010. Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr. Biol. 20:2131–36 [Google Scholar]
  65. Sundaresan NR, Vasudevan P, Zhong L, Kim G, Samant S. 65.  et al. 2012. The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nat. Med. 18:1643–50 [Google Scholar]
  66. Berman JR, Kenyon C. 66.  2006. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124:1055–68 [Google Scholar]
  67. Honda Y, Honda S. 67.  1999. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13:1385–93 [Google Scholar]
  68. Lithgow GJ, White TM, Melov S, Johnson TE. 68.  1995. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. PNAS 92:7540–44 [Google Scholar]
  69. Murakami S, Johnson TE. 69.  1996. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143:1207–18 [Google Scholar]
  70. Singh V, Aballay A. 70.  2006. Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. PNAS 103:13092–97 [Google Scholar]
  71. Barsyte D, Lovejoy DA, Lithgow GJ. 71.  2001. Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J. 15:627–34 [Google Scholar]
  72. Bjedov I, Partridge L. 72.  2011. A longer and healthier life with TOR down-regulation: genetics and drugs. Biochem. Soc. Trans. 39:460–65 [Google Scholar]
  73. Sengupta S, Peterson TR, Sabatini DM. 73.  2010. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 40:310–22 [Google Scholar]
  74. Hsu AL, Murphy CT, Kenyon C. 74.  2003. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–45 [Google Scholar]
  75. Morimoto RI. 75.  1998. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 12:3788–96 [Google Scholar]
  76. Morley JF, Brignull HR, Weyers JJ, Morimoto RI. 76.  2002. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. PNAS 99:10417–22 [Google Scholar]
  77. Lindquist S. 77.  1986. The heat-shock response. Annu. Rev. Biochem. 55:1151–91 [Google Scholar]
  78. Walter P, Ron D. 78.  2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–86 [Google Scholar]
  79. Haynes CM, Ron D. 79.  2010. The mitochondrial UPR—protecting organelle protein homeostasis. J. Cell Sci. 123:3849–55 [Google Scholar]
  80. Henis-Korenblit S, Zhang P, Hansen M, McCormick M, Lee SJ. 80.  et al. 2010. Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. PNAS 107:9730–35 [Google Scholar]
  81. Morley JF, Morimoto RI. 81.  2004. Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol. Biol. Cell 15:657–64 [Google Scholar]
  82. Durieux J, Wolff S, Dillin A. 82.  2011. The cell-non-autonomous nature of electron transport chain–mediated longevity. Cell 144:79–91Reveals that ETC-mediated longevity relies on intertissue signaling. [Google Scholar]
  83. Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S. 83.  et al. 2014. Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans. Nat. Commun. 5:3483 [Google Scholar]
  84. Ben-Zvi A, Miller EA, Morimoto RI. 84.  2009. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. PNAS 106:14914–19 [Google Scholar]
  85. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C. 85.  2010. Widespread protein aggregation as an inherent part of aging in C. elegans. PLOS Biol. 8:e1000450 [Google Scholar]
  86. Mori I, Ohshima Y. 86.  1995. Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 376:344–48 [Google Scholar]
  87. Prahlad V, Cornelius T, Morimoto RI. 87.  2008. Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons. Science 320:811–14Reports that HSR activation in the soma is governed by neurons. [Google Scholar]
  88. Inada H, Ito H, Satterlee J, Sengupta P, Matsumoto K, Mori I. 88.  2006. Identification of guanylyl cyclases that function in thermosensory neurons of Caenorhabditis elegans. Genetics 172:2239–52 [Google Scholar]
  89. Calixto A, Chelur D, Topalidou I, Chen X, Chalfie M. 89.  2010. Enhanced neuronal RNAi in C. elegans using SID-1. Nat. Methods 7:554–59 [Google Scholar]
  90. Maman M, Carvalhal Marques F, Volovik Y, Dubnikov T, Bejerano-Sagie M, Cohen E. 90.  2013. A neuronal GPCR is critical for the induction of the heat shock response in the nematode C. elegans. J. Neurosci. 33:6102–11 [Google Scholar]
  91. Hobert O, D'Alberti T, Liu Y, Ruvkun G. 91.  1998. Control of neural development and function in a thermoregulatory network by the LIM homeobox gene lin-11. J. Neurosci. 18:2084–96 [Google Scholar]
  92. Sun J, Singh V, Kajino-Sakamoto R, Aballay A. 92.  2011. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332:729–32 [Google Scholar]
  93. Taylor RC, Dillin A. 93.  2013. XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153:1435–47 [Google Scholar]
  94. Garcia SM, Casanueva MO, Silva MC, Amaral MD, Morimoto RI. 94.  2007. Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells. Genes Dev. 21:3006–16 [Google Scholar]
  95. Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, Ron D. 95.  2004. Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J. Cell Sci. 117:4055–66 [Google Scholar]
  96. Pellegrino MW, Nargund AM, Haynes CM. 96.  2013. Signaling the mitochondrial unfolded protein response. Biochim. Biophys. Acta 1833:410–16 [Google Scholar]
  97. Libina N, Berman JR, Kenyon C. 97.  2003. Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115:489–502 [Google Scholar]
  98. Alic N, Tullet JM, Niccoli T, Broughton S, Hoddinott MP. 98.  et al. 2014. Cell-nonautonomous effects of dFOXO/DAF-16 in aging. Cell Rep. 6:608–16 [Google Scholar]
  99. Zhang P, Judy M, Lee SJ, Kenyon C. 99.  2013. Direct and indirect gene regulation by a life-extending FOXO protein in C. elegans: roles for GATA factors and lipid gene regulators. Cell Metab. 17:85–100Indicates that DAF-16/FoxO regulates gene expression in cell-autonomous and cell-nonautonomous fashions. [Google Scholar]
  100. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS. 100.  et al. 2003. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–83 [Google Scholar]
  101. Broue F, Liere P, Kenyon C, Baulieu EE. 101.  2007. A steroid hormone that extends the lifespan of Caenorhabditis elegans. Aging Cell 6:87–94 [Google Scholar]
  102. Shemesh N, Shai N, Ben-Zvi A. 102.  2013. Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood. Aging Cell 12:814–22 [Google Scholar]
  103. Boulias K, Horvitz HR. 103.  2012. The C. elegans microRNA mir-71 acts in neurons to promote germline-mediated longevity through regulation of DAF-16/FOXO. Cell Metab. 15:439–50 [Google Scholar]
  104. van Oosten-Hawle P, Porter RS, Morimoto RI. 104.  2013. Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153:1366–78 [Google Scholar]
  105. Hartl FU, Bracher A, Hayer-Hartl M. 105.  2011. Molecular chaperones in protein folding and proteostasis. Nature 475:324–32 [Google Scholar]
  106. Kopito RR, Ron D. 106.  2000. Conformational disease. Nat. Cell Biol. 2:E207–9 [Google Scholar]
  107. Selkoe DJ. 107.  2011. Alzheimer's disease. Cold Spring Harb. Perspect. Biol. 3:a004457 [Google Scholar]
  108. Bates G. 108.  2003. Huntingtin aggregation and toxicity in Huntington's disease. Lancet 361:1642–44 [Google Scholar]
  109. Robberecht W, Philips T. 109.  2013. The changing scene of amyotrophic lateral sclerosis. Nat. Rev. Neurosci. 14:248–64 [Google Scholar]
  110. Aguzzi A, Calella AM. 110.  2009. Prions: protein aggregation and infectious diseases. Physiol. Rev. 89:1105–52 [Google Scholar]
  111. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE. 111.  et al. 2008. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14:837–42Reports that small oligomers are the most toxic Aβ species. [Google Scholar]
  112. O'Nuallain B, Freir DB, Nicoll AJ, Risse E, Ferguson N. 112.  et al. 2010. Amyloid β-protein dimers rapidly form stable synaptotoxic protofibrils. J. Neurosci. 30:14411–19 [Google Scholar]
  113. Silveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL. 113.  et al. 2005. The most infectious prion protein particles. Nature 437:257–61 [Google Scholar]
  114. Durcan TM, Fon EA. 114.  2013. Ataxin-3 and its E3 partners: implications for Machado–Joseph disease. Front. Neurol. 4:46 [Google Scholar]
  115. Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC. 115.  et al. 2006. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–33 [Google Scholar]
  116. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P. 116.  et al. 1993. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62 [Google Scholar]
  117. Amaducci L, Tesco G. 117.  1994. Aging as a major risk for degenerative diseases of the central nervous system. Curr. Opin. Neurol. 7:283–86 [Google Scholar]
  118. Balch WE, Morimoto RI, Dillin A, Kelly JW. 118.  2008. Adapting proteostasis for disease intervention. Science 319:916–19 [Google Scholar]
  119. Volovik Y, Carvalhal Marques F, Cohen E. 119.  2014. The nematode Caenorhabditis elegans: a versatile model for the study of proteotoxicity and aging. Methods 68:458–64 [Google Scholar]
  120. Li J, Le W. 120.  2013. Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp. Neurol. 250:94–103 [Google Scholar]
  121. Link C. 121.  1995. Expression of human β-amyloid peptide in transgenic Caenorhabditis elegans. PNAS 92:9368–72 [Google Scholar]
  122. McColl G, Roberts BR, Gunn AP, Perez KA, Tew DJ. 122.  et al. 2009. The Caenorhabditis elegans Aβ1–42 model of Alzheimer disease predominantly expresses Aβ3–42. J. Biol. Chem. 284:22697–702 [Google Scholar]
  123. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A. 123.  2006. Opposing activities protect against age-onset proteotoxicity. Science 313:1604–10Demonstrates that slowing aging by IIS reduction alleviates Aβ proteotoxicity. [Google Scholar]
  124. Cohen E, Du D, Joyce D, Kapernick EA, Volovik Y. 124.  et al. 2010. Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection. Aging Cell 9:126–34 [Google Scholar]
  125. Dillin A, Crawford DK, Kenyon C. 125.  2002. Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298:830–34 [Google Scholar]
  126. Volovik Y, Maman M, Dubnikov T, Bejerano-Sagie M, Joyce D. 126.  et al. 2012. Temporal requirements of heat shock factor-1 for longevity assurance. Aging Cell 11:491–99 [Google Scholar]
  127. Cohen E, Dillin A. 127.  2008. The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat. Rev. Neurosci. 9:759–67 [Google Scholar]
  128. Steinkraus KA, Smith ED, Davis C, Carr D, Pendergrass WR. 128.  et al. 2008. Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7:394–404 [Google Scholar]
  129. Mouton PR, Chachich ME, Quigley C, Spangler E, Ingram DK. 129.  2009. Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci. Lett. 464:184–87 [Google Scholar]
  130. Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T. 130.  et al. 2006. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351:602–11 [Google Scholar]
  131. Zhang T, Mullane PC, Periz G, Wang J. 131.  2011. TDP-43 neurotoxicity and protein aggregation modulated by heat shock factor and insulin/IGF-1 signaling. Hum. Mol. Genet. 20:1952–65 [Google Scholar]
  132. Boccitto M, Lamitina T, Kalb RG. 132.  2012. Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans. PLOS ONE 7:e33494 [Google Scholar]
  133. Teixeira-Castro A, Ailion M, Jalles A, Brignull HR, Vilaca JL. 133.  et al. 2011. Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways. Hum. Mol. Genet. 20:2996–3009 [Google Scholar]
  134. Killick R, Scales G, Leroy K, Causevic M, Hooper C. 134.  et al. 2009. Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem. Biophys. Res. Commun. 386:257–62 [Google Scholar]
  135. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y. 135.  et al. 1996. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99–102 [Google Scholar]
  136. Freude S, Hettich MM, Schumann C, Stohr O, Koch L. 136.  et al. 2009. Neuronal IGF-1 resistance reduces Aβ accumulation and protects against premature death in a model of Alzheimer's disease. FASEB J. 23:3315–24 [Google Scholar]
  137. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR. 137.  2001. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol. Eng. 17:157–65 [Google Scholar]
  138. Reiserer RS, Harrison FE, Syverud DC, McDonald MP. 138.  2007. Impaired spatial learning in the APPSwe + PSEN1ΔE9 bigenic mouse model of Alzheimer's disease. Genes Brain Behav. 6:54–65 [Google Scholar]
  139. Cohen E, Paulsson JF, Blinder P, Burstyn-Cohen T, Du D. 139.  et al. 2009. Reduced IGF-1 signaling delays age-associated proteotoxicity in mice. Cell 139:1157–69 [Google Scholar]
  140. Haass C, Selkoe DJ. 140.  2007. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nat. Rev. Mol. Cell Biol. 8:101–12 [Google Scholar]
  141. Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I. 141.  2002. Serum insulin-like growth factor I regulates brain amyloid-β levels. Nat. Med. 8:1390–97 [Google Scholar]
  142. Fernandez AM, Torres-Aleman I. 142.  2012. The many faces of insulin-like peptide signalling in the brain. Nat. Rev. Neurosci. 13:225–39 [Google Scholar]
  143. Prahlad V, Morimoto RI. 143.  2011. Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins. PNAS 108:14204–9 [Google Scholar]
  144. Van Raamsdonk JM, Hekimi S. 144.  2009. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLOS Genet. 5:e1000361 [Google Scholar]
  145. Van Raamsdonk JM, Hekimi S. 145.  2012. Superoxide dismutase is dispensable for normal animal lifespan. PNAS 109:5785–90 [Google Scholar]
  146. Calamini B, Silva MC, Madoux F, Hutt DM, Khanna S. 146.  et al. 2012. Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol. 8:185–96 [Google Scholar]
  147. Mendillo ML, Santagata S, Koeva M, Bell GW, Hu R. 147.  et al. 2012. HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell 150:549–62 [Google Scholar]
  148. Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R. 148.  et al. 2013. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 73:4383–94 [Google Scholar]
  149. El-Ami T, Moll L, Carvalhal Marques F, Volovik Y, Reuveni H, Cohen E. 149.  2014. A novel inhibitor of the insulin/IGF signaling pathway protects from age-onset, neurodegeneration-linked proteotoxicity. Aging Cell 13:165–74 [Google Scholar]
  150. Soto C. 150.  2003. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci. 4:49–60 [Google Scholar]
  151. Ben-Gedalya T, Cohen E. 151.  2012. Quality control compartments coming of age. Traffic 13:635–42 [Google Scholar]
  152. Taylor RC, Berendzen KM, Dillin A. 152.  2014. Systemic stress signalling: understanding the cell non-autonomous control of proteostasis. Nat. Rev. Mol. Cell Biol. 15:211–17 [Google Scholar]
  153. Dingley S, Polyak E, Lightfoot R, Ostrovsky J, Rao M. 153.  et al. 2010. Mitochondrial respiratory chain dysfunction variably increases oxidant stress in Caenorhabditis elegans. Mitochondrion 10:125–36 [Google Scholar]
  154. Blüher M, Kahn BB, Kahn CR. 154.  2003. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–74 [Google Scholar]
  155. Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M. 155.  et al. 2008. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 22:807–18 [Google Scholar]
  156. Lakowski B, Hekimi S. 156.  1998. The genetics of caloric restriction in Caenorhabditis elegans. PNAS 95:13091–96 [Google Scholar]
  157. Patel DS, Garza-Garcia A, Nanji M, McElwee JJ, Ackerman D. 157.  et al. 2008. Clustering of genetically defined allele classes in the Caenorhabditis elegans DAF-2 insulin/IGF-1 receptor. Genetics 178:931–46 [Google Scholar]
  158. Ladiges W, Van Remmen H, Strong R, Ikeno Y, Treuting P. 158.  et al. 2009. Lifespan extension in genetically modified mice. Aging Cell 8:346–52 [Google Scholar]
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The Roles of Cellular and Organismal Aging in the Development of Late-Onset Maladies
Annual Review of Pathology: Mechanisms of Disease 10, 1 (2015); https://doi.org/10.1146/annurev-pathol-012414-040508
/content/journals/10.1146/annurev-pathol-012414-040508
/content/journals/10.1146/annurev-pathol-012414-040508
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