The age- and sex-specific decline of the 20s proteasome and the Nrf2/CncC signal transduction pathway in adaption and resistance to oxidative stress in Drosophila melanogaster

Aging

Volumn 9, Issue 4, 2017, Pages 1153-1185

  Pomatto, Laura C D ^a   Wong, Sarah ^a   Carney, Caroline ^a   Shen, Brenda ^a   Tower, John ^a,b   Davies, Kelvin J A ^a,b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

20S proteasome; Adaptive homeostasis; Nrf2; Oxidative stress; Protein aggregation; Protein oxidation

Indexed keywords

ADENOSINE TRIPHOSPHATE; CAP-N-COLLAR PROTEIN, DROSOPHILA; DROSOPHILA PROTEIN; HYDROGEN PEROXIDE; KEAP1 PROTEIN, DROSOPHILA; KELCH LIKE ECH ASSOCIATED PROTEIN 1; PROTEASOME; REPRESSOR PROTEIN;

ADAPTATION; AGING; ANIMAL; BIOSYNTHESIS; DROSOPHILA MELANOGASTER; FEMALE; GENE EXPRESSION REGULATION; GENE KNOCKDOWN; GENETICS; MALE; METABOLISM; OXIDATIVE STRESS; PROTEIN CARBONYLATION; SEXUAL CHARACTERISTICS; SIGNAL TRANSDUCTION;

ADAPTATION, PHYSIOLOGICAL; ADENOSINE TRIPHOSPHATE; AGING; ANIMALS; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE KNOCKDOWN TECHNIQUES; HYDROGEN PEROXIDE; KELCH-LIKE ECH-ASSOCIATED PROTEIN 1; MALE; OXIDATIVE STRESS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN CARBONYLATION; REPRESSOR PROTEINS; SEX CHARACTERISTICS; SIGNAL TRANSDUCTION;

EID: 85018942373     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.101218     Document Type: Article

References (108)

1. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002; 82:47-95. doi: 10.1152/physrev.00018.2001.
2. Squier TC. Oxidative stress and protein aggregation during biological aging. Exp Gerontol. 2001; 36:1539-50 doi: 10.1016/S0531-5565(01)00139-5.
3. Tanase M, Urbanska AM, Zolla V, Clement CC, Huang L, Morozova K, Follo C, Goldberg M, Roda B, Reschiglian P, Santambrogio L. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation. Sci Rep. 2016; 6:19311. doi: 10.1038/srep19311.
4. Davies KJ. Degradation of oxidized proteins by the 20S proteasome. Biochimie. 2001; 83:301-10. doi: 10.1016/S0300-9084(01)01250-0.
5. Grune T, Reinheckel T, Davies KJ. Degradation of oxidized proteins in mammalian cells. FASEB J. 1997; 11:526-34. 10.1002/biof.5520060210.
6. Grune T, Reinheckel T, Davies KJ. Degradation of oxidized proteins in K562 human hematopoietic cells by proteasome. J Biol Chem. 1996; 271:15504-09. doi: 10.1074/jbc.271.26.15504.
7. Bota DA, Davies KJ. Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATPstimulated mechanism. Nat Cell Biol. 2002; 4:674-80. doi: 10.1038/ncb836.
8. Davies KJ. Adaptive homeostasis. Mol Aspects Med. 2016; 49:1-7. doi: 10.1016/j.mam.2016.04.007.
9. Davies JM, Lowry CV, Davies KJ. Transient adaptation to oxidative stress in yeast. Arch Biochem Biophys. 1995; 317:1-6. doi: 10.1006/abbi.1995.1128.
10. Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sánchez-Pérez P, Cadenas S, Lamas S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015; 6:183-97. doi: 10.1016/j.redox.2015.07.008.
11. Haigis MC, Yankner BA. The aging stress response. Mol Cell. 2010; 40:333-44. doi: 10.1016/j.molcel.2010.10.002.
12. Ben-Zvi A, Miller EA, Morimoto RI. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci USA. 2009; 106:14914-19. doi: 10.1073/pnas.0902882106.
13. Reis-Rodrigues P, Czerwieniec G, Peters TW, Evani US, Alavez S, Gaman EA, Vantipalli M, Mooney SD, Gibson BW, Lithgow GJ, Hughes RE. Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan. Aging Cell. 2012; 11:120-27. doi: 10.1111/j.1474-9726.2011.00765.x.
14. Lewis KN, Wason E, Edrey YH, Kristan DM, Nevo E, Buffenstein R. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci USA. 2015; 112:3722-27. doi: 10.1073/pnas.1417566112.
15. Pickering AM, Lehr M, Kohler WJ, Han ML, Miller RA. Fibroblasts from longer-lived species of primates, rodents, bats, carnivores, and birds resist protein damage. J Gerontol A Biol Sci Med Sci. 2015; 70:791-99 doi: 10.1093/gerona/glu115.
16. Chondrogianni N, Petropoulos I, Franceschi C, Friguet B, Gonos ES. Fibroblast cultures from healthy centenarians have an active proteasome. Exp Gerontol. 2000; 35:721-28. doi: 10.1016/S0531-5565(00)00137-6.
17. Pickering AM, Davies KJ. Degradation of damaged proteins: the main function of the 20S proteasome. Prog Mol Biol Transl Sci. 2012; 109:227-48. doi: 10.1016/B978-0-12-397863-9.00006-7.
18. Raynes R, Pomatto LC, Davies KJ. Degradation of oxidized proteins by the proteasome: distinguishing between the 20S, 26S, and immunoproteasome proteolytic pathways. Mol Aspects Med. 2016; 50:41-55 doi: 10.1016/j.mam.2016.05.001.
19. Pan JX, Short SR, Goff SA, Dice JF. Ubiquitin pools, ubiquitin mRNA levels, and ubiquitin-mediated proteolysis in aging human fibroblasts. Exp Gerontol. 1993; 28:39-49. doi: 10.1016/0531-5565(93)90018-9.
20. Vernace VA, Arnaud L, Schmidt-Glenewinkel T, Figueiredo-Pereira ME. Aging perturbs 26S proteasome assembly in Drosophila melanogaster. FASEB J. 2007; 21:2672-82. doi: 10.1096/fj.06-6751com.
21. Demontis F, Piccirillo R, Goldberg AL, Perrimon N. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models. Dis Model Mech. 2013; 6:1339-52. doi: 10.1242/dmm.012559.
22. Silva GM, Finley D, Vogel C. K63 polyubiquitination is a new modulator of the oxidative stress response. Nat Struct Mol Biol. 2015; 22:116-23. http://www.nature.com/nsmb/journal/v22/n2/abs/n smb.2955.html#supplementary-information doi: 10.1038/nsmb.2955.
23. Pickering AM, Koop AL, Teoh CY, Ermak G, Grune T, Davies KJ. The immunoproteasome, the 20S proteasome and the PA28αβ proteasome regulator are oxidative-stress-adaptive proteolytic complexes. Biochem J. 2010; 432:585-94. doi: 10.1042/BJ20100878.
24. Shringarpure R, Grune T, Mehlhase J, Davies KJ. Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome. J Biol Chem. 2003; 278:311-18. doi: 10.1074/jbc.M206279200.
25. Wiggins CM, Tsvetkov P, Johnson M, Joyce CL, Lamb CA, Bryant NJ, Komander D, Shaul Y, Cook SJ. BIM(EL), an intrinsically disordered protein, is degraded by 20S proteasomes in the absence of poly-ubiquitylation. J Cell Sci. 2011; 124:969-77. doi: 10.1242/jcs.058438.
26. Shang F, Taylor A. Oxidative stress and recovery from oxidative stress are associated with altered ubiquitin conjugating and proteolytic activities in bovine lens epithelial cells. Biochem J. 1995; 307:297-303. doi: 10.1042/bj3070297.
27. Grune T, Catalgol B, Licht A, Ermak G, Pickering AM, Ngo JK, Davies KJ. HSP70 mediates dissociation and reassociation of the 26S proteasome during adaptation to oxidative stress. Free Radic Biol Med. 2011; 51:1355-64. doi: 10.1016/j.freeradbiomed.2011.06.015.
28. Wang X, Yen J, Kaiser P, Huang L. Regulation of the 26S proteasome complex during oxidative stress. Sci Signal. 2010; 3:ra88. doi: 10.1126/scisignal.2001232.
29. Cook C, Gass J, Dunmore J, Tong J, Taylor J, Eriksen J, McGowan E, Lewis J, Johnston J, Petrucelli L. Aging is not associated with proteasome impairment in UPS reporter mice. PLoS One. 2009; 4:e5888. doi: 10.1371/journal.pone.0005888.
30. Reinheckel T, Sitte N, Ullrich O, Kuckelkorn U, Davies KJ, Grune T. Comparative resistance of the 20S and 26S proteasome to oxidative stress. Biochem J. 1998; 335:637-42. doi: 10.1042/bj3350637.
31. Sahakian JA, Szweda LI, Friguet B, Kitani K, Levine RL. Aging of the liver: proteolysis of oxidatively modified glutamine synthetase. Arch Biochem Biophys. 1995; 318:411-17. doi: 10.1006/abbi.1995.1248.
32. Bonduriansky R, Maklakov A, Zajitschek F, Brooks R. Sexual selection, sexual conflict and the evolution of ageing and life span. Funct Ecol. 2008; 22:443-53. doi doi: 10.1111/j.1365-2435.2008.01417.x.
33. Finch CE, Tower J. Sex-specific aging in flies, worms, and missing great-granddads. Cell. 2014; 156:398-99. doi: 10.1016/j.cell.2014.01.028.
34. Tower J. Sex-specific regulation of aging and apoptosis. Mech Ageing Dev. 2006; 127:705-18. doi: 10.1016/j.mad.2006.05.001.
35. Camus MF, Clancy DJ, Dowling DK. Mitochondria, maternal inheritance, and male aging. Curr Biol. 2012; 22:1717-21. doi: 10.1016/j.cub.2012.07.018.
36. Shen J, Landis GN, Tower J. Multiple Metazoan Lifespan Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration. J Gerontol A Biol Sci Med Sci. 2017; 72:44-53. doi: 10.1093/gerona/glw005.
37. Tower J. Mitochondrial maintenance failure in aging and role of sexual dimorphism. Arch Biochem Biophys. 2015; 576:17-31. doi: 10.1016/j.abb.2014.10.008.
38. Holzenberger M, Dupont J, Ducos B, Leneuve P, Géloën A, Even PC, Cervera P, Le Bouc Y. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003; 421:182-87. doi: 10.1038/nature01298.
39. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, et al. Rapamycinmediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell. 2014; 13:468-77. doi: 10.1111/acel.12194.
40. Seifarth JE, McGowan CL, Milne KJ. Sex and life expectancy. Gend Med. 2012; 9:390-401. doi: 10.1016/j.genm.2012.10.001.
41. Minois N, Carmona-Gutierrez D, Bauer MA, Rockenfeller P, Eisenberg T, Brandhorst S, Sigrist SJ, Kroemer G, Madeo F. Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and-independent pathways. Cell Death Dis. 2012; 3:e401. doi: 10.1038/cddis.2012.139.
42. Ross JL, Howlett SE. Age and ovariectomy abolish beneficial effects of female sex on rat ventricular myocytes exposed to simulated ischemia and reperfusion. PLoS One. 2012; 7:e38425. doi: 10.1371/journal.pone.0038425.
43. Pickering AM, Staab TA, Tower J, Sieburth D, Davies KJ. A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative stress adaptation in mammals, Caenorhabditis elegans and Drosophila melanogaster. J Exp Biol. 2013; 216:543-53. doi: 10.1242/jeb.074757.
44. Pickering AM, Vojtovich L, Tower J, A Davies KJ. Oxidative stress adaptation with acute, chronic, and repeated stress. Free Radic Biol Med. 2013; 55:109-18 doi: 10.1016/j.freeradbiomed.2012.11.001.
45. Semenchenko GV, Khazaeli AA, Curtsinger JW, Yashin AI. Stress resistance declines with age: analysis of data from a survival experiment with Drosophila melanogaster. Biogerontology. 2004; 5:17-30. doi: 10.1023/B:BGEN.0000017681.46326.9e.
46. Wang MC, Bohmann D, Jasper H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell. 2003; 5:811-16. doi: 10.1016/S1534-5807(03)00323-X.
47. Pomatto LC, Carney C, Shen B, Wong S, Halaszynski K, Salomon MP, Davies KJ, Tower J. The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress. Curr Biol. 2017; 27:1-15. doi: 10.1016/j.cub.2016.10.044.
48. Landis GN, Salomon MP, Keroles D, Brookes N, Sekimura T, Tower J. The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila. Aging (Albany NY). 2015; 7:53-69. doi: 10.18632/aging.100721.
49. Landis GN, Abdueva D, Skvortsov D, Yang J, Rabin BE, Carrick J, Tavaré S, Tower J. Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster. Proc Natl Acad Sci USA. 2004; 101:7663-68. doi: 10.1073/pnas.0307605101.
50. Wiese AG, Pacifici RE, Davies KJ. Transient adaptation of oxidative stress in mammalian cells. Arch Biochem Biophys. 1995; 318:231-40. doi: 10.1006/abbi.1995.1225.
51. Pickering AM, Linder RA, Zhang H, Forman HJ, Davies KJ. Nrf2-dependent induction of proteasome and Pa28αβ regulator are required for adaptation to oxidative stress. J Biol Chem. 2012; 287:10021-31. doi: 10.1074/jbc.M111.277145.
52. Divald A, Powell SR. Proteasome mediates removal of proteins oxidized during myocardial ischemia. Free Radic Biol Med. 2006; 40:156-64. doi: 10.1016/j.freeradbiomed.2005.09.022.
53. Raynes R, Juarez C, Pomatto LC, Sieburth D, Davies KJ. Aging and SKN-1-dependent Loss of 20S Proteasome Adaptation to Oxidative Stress in C. elegans. J Gerontol A Biol Sci Med Sci. 2017; 72:143-51. doi: 10.1093/gerona/glw093.
54. Pickering AM, Davies KJ. Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins. Arch Biochem Biophys. 2012; 523:181-90. doi: 10.1016/j.abb.2012.04.018.
55. Grune T, Jung T, Merker K, Davies KJ. Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease. Int J Biochem Cell Biol. 2004; 36:2519-30. doi: 10.1016/j.biocel.2004.04.020.
56. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol. 2010; 8:e1000450. doi: 10.1371/journal.pbio.1000450.
57. Tsakiri EN, Sykiotis GP, Papassideri IS, Gorgoulis VG, Bohmann D, Trougakos IP. Differential regulation of proteasome functionality in reproductive vs. somatic tissues of Drosophila during aging or oxidative stress. FASEB J. 2013; 27:2407-20. doi: 10.1096/fj.12-221408.
58. Gohlke S, Mishto M, Textoris-Taube K, Keller C, Giannini C, Vasuri F, Capizzi E, D'Errico-Grigioni A, Kloetzel PM, Dahlmann B. Molecular alterations in proteasomes of rat liver during aging result in altered proteolytic activities. Age (Dordr). 2014; 36:57-72. doi: 10.1007/s11357-013-9543-x.
59. Louie JL, Kapphahn RJ, Ferrington DA. Proteasome function and protein oxidation in the aged retina. Exp Eye Res. 2002; 75:271-84. doi: 10.1016/S0014-4835(02)92022-1.
60. Petersen A, Honarvar A, Zetterberg M. Changes in activity and kinetic properties of the proteasome in different rat organs during development and maturation. Curr Gerontol Geriatr Res. 2010; 2010:230697. doi: 10.1155/2010/230697.
61. Caniard A, Ballweg K, Lukas C, Yildirim Aö, Eickelberg O, Meiners S. Proteasome function is not impaired in healthy aging of the lung. Aging (Albany NY). 2015; 7:776-92. doi: 10.18632/aging.100820.
62. Ford D, Hoe N, Landis GN, Tozer K, Luu A, Bhole D, Badrinath A, Tower J. Alteration of Drosophila life span using conditional, tissue-specific expression of transgenes triggered by doxycyline or RU486/Mifepristone. Exp Gerontol. 2007; 42:483-97. doi: 10.1016/j.exger.2007.01.004.
63. Breusing N, Arndt J, Voss P, Bresgen N, Wiswedel I, Gardemann A, Siems W, Grune T. Inverse correlation of protein oxidation and proteasome activity in liver and lung. Mech Ageing Dev. 2009; 130:748-53. doi: 10.1016/j.mad.2009.09.004.
64. Ngo JK, Davies KJ. Mitochondrial Lon protease is a human stress protein. Free Radic Biol Med. 2009; 46:1042-48. doi: 10.1016/j.freeradbiomed.2008.12.024.
65. Ngo JK, Pomatto LC, Bota DA, Koop AL, Davies KJ. Impairment of lon-induced protection against the accumulation of oxidized proteins in senescent wi-38 fibroblasts. J Gerontol A Biol Sci Med Sci. 2011; 66:1178-85. doi: 10.1093/gerona/glr145.
66. Stadtman ER, Levine RL. Free radical-mediated oxidation of free amino acids and amino acid residues in proteins. Amino Acids. 2003; 25:207-18. doi: 10.1007/s00726-003-0011-2.
67. Chen P, Hochstrasser M. Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly. Cell. 1996; 86:961-72. doi: 10.1016/S0092-8674(00)80171-3.
68. Tsakiri EN, Sykiotis GP, Papassideri IS, Terpos E, Dimopoulos MA, Gorgoulis VG, Bohmann D, Trougakos IP. Proteasome dysfunction in Drosophila signals to an Nrf2-dependent regulatory circuit aiming to restore proteostasis and prevent premature aging. Aging Cell. 2013; 12:802-13. doi: 10.1111/acel.12111.
69. Ren C, Finkel SE, Tower J. Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity. Exp Gerontol. 2009; 44:228-35. doi: 10.1016/j.exger.2008.10.002.
70. Sykiotis GP, Bohmann D. Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila. Dev Cell. 2008; 14:76-85. doi: 10.1016/j.devcel.2007.12.002.
71. Beedholm R, Clark BF, Rattan SI. Mild heat stress stimulates 20S proteasome and its 11S activator in human fibroblasts undergoing aging in vitro. Cell Stress Chaperones. 2004; 9:49-57. doi: 10.1379/1466-1268(2004)009<0049:MHSSSP>2.0.CO;2.
72. Lithgow GJ, White TM, Melov S, Johnson TE. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA. 1995; 92:7540-44. doi: 10.1073/pnas.92.16.7540.
73. Moskalev A, Shaposhnikov M, Turysheva E. Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps. Biogerontology. 2009; 10:3-11. doi: 10.1007/s10522-008-9147-5.
74. Cypser JR, Johnson TE. Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J Gerontol A Biol Sci Med Sci. 2002; 57:B109-14. doi: 10.1093/gerona/57.3.B109.
75. Grune T, Merker K, Sandig G, Davies KJ. Selective degradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun. 2003; 305:709-18. doi: 10.1016/S0006-291X(03)00809-X.
76. Shringarpure R, Grune T, Davies KJ. Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells. Cell Mol Life Sci. 2001; 58:1442-50. doi: 10.1007/PL00000787.
77. Sitte N, Huber M, Grune T, Ladhoff A, Doecke WD, Von Zglinicki T, Davies KJ. Proteasome inhibition by lipofuscin/ceroid during postmitotic aging of fibroblasts. FASEB J. 2000; 14:1490-98. doi: 10.1096/fj.14.11.1490.
78. Rodriguez KA, Gaczynska M, Osmulski PA. Molecular mechanisms of proteasome plasticity in aging. Mech Ageing Dev. 2010; 131:144-55. doi: 10.1016/j.mad.2010.01.002.
79. Ferrington DA, Husom AD, Thompson LV. Altered proteasome structure, function, and oxidation in aged muscle. FASEB J. 2005; 19:644-46. 10.1096/fj.04-2578fje.
80. Husom AD, Peters EA, Kolling EA, Fugere NA, Thompson LV, Ferrington DA. Altered proteasome function and subunit composition in aged muscle. Arch Biochem Biophys. 2004; 421:67-76. doi: 10.1016/j.abb.2003.10.010.
81. Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem. 2000; 75:436-39. doi: 10.1046/j.1471-4159.2000.0750436.x.
82. Hayashi T, Goto S. Age-related changes in the 20S and 26S proteasome activities in the liver of male F344 rats. Mech Ageing Dev. 1998; 102:55-66. doi: 10.1016/S0047-6374(98)00011-6.
83. Bulteau AL, Szweda LI, Friguet B. Age-dependent declines in proteasome activity in the heart. Arch Biochem Biophys. 2002; 397:298-304. doi: 10.1006/abbi.2001.2663.
84. Oliver CN, Ahn BW, Moerman EJ, Goldstein S, Stadtman ER. Age-related changes in oxidized proteins. J Biol Chem. 1987; 262:5488-91. 10.1016/s0891-5849(99)90520-8.
85. Powell SR, Wang P, Divald A, Teichberg S, Haridas V, McCloskey TW, Davies KJ, Katzeff H. Aggregates of oxidized proteins (lipofuscin) induce apoptosis through proteasome inhibition and dysregulation of proapoptotic proteins. Free Radic Biol Med. 2005; 38:1093-101. doi: 10.1016/j.freeradbiomed.2005.01.003.
86. Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, Markesbery WR. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA. 1991; 88:10540-43. doi: 10.1073/pnas.88.23.10540.
87. Tseng BP, Green KN, Chan JL, Blurton-Jones M, LaFerla FM. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging. 2008; 29:1607-18. doi: 10.1016/j.neurobiolaging.2007.04.014.
88. Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem. 2000; 75:436-39. doi: 10.1046/j.1471-4159.2000.0750436.x.
89. Cecarini V, Ding Q, Keller JN. Oxidative inactivation of the proteasome in Alzheimer's disease. Free Radic Res. 2007; 41:673-80. doi: 10.1080/10715760701286159.
90. Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010; 464:529-35 doi: 10.1038/nature08983.
91. Bulteau AL, Petropoulos I, Friguet B. Age-related alterations of proteasome structure and function in aging epidermis. Exp Gerontol. 2000; 35:767-77. doi: 10.1016/S0531-5565(00)00136-4.
92. Cochemé HM, Quin C, McQuaker SJ, Cabreiro F, Logan A, Prime TA, Abakumova I, Patel JV, Fearnley IM, James AM, Porteous CM, Smith RA, Saeed S, et al. Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab. 2011; 13:340-50. doi: 10.1016/j.cmet.2011.02.003.
93. Craiu A, Gaczynska M, Akopian T, Gramm CF, Fenteany G, Goldberg AL, Rock KL. Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation. J Biol Chem. 1997; 272:13437-45. doi: 10.1074/jbc.272.20.13437.
94. Lee DH, Goldberg AL. Selective inhibitors of the proteasome-dependent and vacuolar pathways of protein degradation in Saccharomyces cerevisiae. J Biol Chem. 1996; 271:27280-84. doi: 10.1074/jbc.271.44.27280.
95. Kisselev AF, Akopian TN, Castillo V, Goldberg AL. Pro teasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown. Mol Cell. 1999; 4:395-402. doi: 10.1016/S1097-2765(00)80341-X.
96. Li Z, Arnaud L, Rockwell P, Figueiredo-Pereira ME. A single amino acid substitution in a proteasome subunit triggers aggregation of ubiquitinated proteins in stressed neuronal cells. J Neurochem. 2004; 90:19-28 doi: 10.1111/j.1471-4159.2004.02456.x.
97. Conconi M, Petropoulos I, Emod I, Turlin E, Biville F, Friguet B. Protection from oxidative inactivation of the 20S proteasome byheat-shock protein 90. Biochem J. 1998; 333:407-15. doi: 10.1042/bj3330407.
98. Magwere T, Chapman T, Partridge L. Sex differences in the effect of dietary restriction on life span and mortality rates in female and male Drosophila melanogaster. J Gerontol A Biol Sci Med Sci. 2004; 59:3-9. doi: 10.1093/gerona/59.1.B3.
99. Anisimov VN, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Egormin PA, Yurova MV, Rosenfeld SV, Semenchenko AV, Kovalenko IG, Poroshina TE, Berstein LM. Gender differences in metformin effect on aging, life span and spontaneous tumorigenesis in 129/Sv mice. Aging (Albany NY). 2010; 2:945-58. doi: 10.18632/aging.100245.
100. Austad SN. Why women live longer than men: sex differences in longevity. Gend Med. 2006; 3:79-92. doi: 10.1016/S1550-8579(06)80198-1.
101. Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó FV, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med. 2003; 34:546-52. doi: 10.1016/S0891-5849(02)01356-4.
102. Pinto RE, Bartley W. The effect of age and sex on glutathione reductase and glutathione peroxidase activities and on aerobic glutathione oxidation in rat liver homogenates. Biochem J. 1969; 112:109-15. doi: 10.1042/bj1120109.
103. Hansen TØ, Sarup P, Loeschcke V, Rattan SI. Agerelated and sex-specific differences in proteasome activity in individual Drosophila flies from wild type, longevity-selected and stress resistant strains. Biogerontology. 2012; 13:429-38. doi: 10.1007/s10522-012-9387-2.
104. Sykiotis GP, Bohmann D. Stress-activated cap'n'collar transcription factors in aging and human disease. Sci Signal. 2010; 3:re3. doi: 10.1126/scisignal.3112re3.
105. Jentoft N, Dearborn DG. Labeling of proteins by reductive methylation using sodium cyanoborohydride. 1979; American Society for Biochemistry and Molecular Biology.
106. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design targetspecific primers for polymerase chain reaction. BMC Bioinformatics. 2012; 13:134. doi: 10.1186/1471-2105-13-134.
107. Ren C, Webster P, Finkel SE, Tower J. Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab. 2007; 6:144-52. doi: 10.1016/j.cmet.2007.06.006.
108. R Development Core Team. R: A language and environment for statistical computing. 2010; (Vienna, Austria: R Foundation for Statistical Computing).