Identification of transcriptomic responses related to normal, healthy and accelerated aging

El envejecimiento es la reducción de las capacidades fisiológicas y adaptativas del organismo con el paso del tiempo. La acumulación de daño en el ADN podría ser el evento central desencadenante del proceso de envejecimiento. Los síndromes progeroides causados por una deficiencia de la sub-vía de re...

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Tipo de recurso:
Fecha de publicación:
2018
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
spa
OAI Identifier:
oai:repository.urosario.edu.co:10336/19101
Acceso en línea:
https://doi.org/10.48713/10336_19101
http://repository.urosario.edu.co/handle/10336/19101
Palabra clave:
Envejecimiento
Transcriptomica
Expectativa de vida
Respuesta protectora
Estrés agudo
Daño en el ADN
Parkinson
Fisiología humana
Aging
DNA damage
lifespan
protective response
Parkinson
Envejecimiento
ADN
Expectativa de vida
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License
Atribución-NoComercial-SinDerivadas 2.5 Colombia
id EDOCUR2_54e920654ca114286d90e3caddc9b3aa
oai_identifier_str oai:repository.urosario.edu.co:10336/19101
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Identification of transcriptomic responses related to normal, healthy and accelerated aging
title Identification of transcriptomic responses related to normal, healthy and accelerated aging
spellingShingle Identification of transcriptomic responses related to normal, healthy and accelerated aging
Envejecimiento
Transcriptomica
Expectativa de vida
Respuesta protectora
Estrés agudo
Daño en el ADN
Parkinson
Fisiología humana
Aging
DNA damage
lifespan
protective response
Parkinson
Envejecimiento
ADN
Expectativa de vida
title_short Identification of transcriptomic responses related to normal, healthy and accelerated aging
title_full Identification of transcriptomic responses related to normal, healthy and accelerated aging
title_fullStr Identification of transcriptomic responses related to normal, healthy and accelerated aging
title_full_unstemmed Identification of transcriptomic responses related to normal, healthy and accelerated aging
title_sort Identification of transcriptomic responses related to normal, healthy and accelerated aging
dc.contributor.advisor.none.fl_str_mv Ramírez Clavijo, Sandra Rocío
dc.subject.spa.fl_str_mv Envejecimiento
Transcriptomica
Expectativa de vida
Respuesta protectora
Estrés agudo
Daño en el ADN
Parkinson
topic Envejecimiento
Transcriptomica
Expectativa de vida
Respuesta protectora
Estrés agudo
Daño en el ADN
Parkinson
Fisiología humana
Aging
DNA damage
lifespan
protective response
Parkinson
Envejecimiento
ADN
Expectativa de vida
dc.subject.ddc.spa.fl_str_mv Fisiología humana
dc.subject.keyword.spa.fl_str_mv Aging
DNA damage
lifespan
protective response
Parkinson
dc.subject.lemb.spa.fl_str_mv Envejecimiento
ADN
Expectativa de vida
description El envejecimiento es la reducción de las capacidades fisiológicas y adaptativas del organismo con el paso del tiempo. La acumulación de daño en el ADN podría ser el evento central desencadenante del proceso de envejecimiento. Los síndromes progeroides causados por una deficiencia de la sub-vía de reparación de escisión de nucleótidos acoplada a transcripción (TCR-NER) presentan un vínculo directo entre daño en el ADN y envejecimiento. Hay un paralelo entre la respuesta transcripcional de ratones progeroides y ratones sometidos a restricción dietética (DR) (una intervención que prolonga la vida). La DR aumenta la resistencia a diferentes formas de estrés. Ratones deficientes en TCR-NER también son menos susceptibles a un tipo de estrés agudo. El paralelo entre las respuestas transcriptómicas de los animales en dos extremos de esperanza de vida se ha explicado por la existencia de una respuesta de supervivencia programada. Esta tesis aborda varias cuestiones relacionadas con la respuesta de supervivencia utilizando principalmente el análisis de datos transcriptómicos. Primero, se estableció que los ratones viejos activan una respuesta de supervivencia incompleta después de tres días de DR, en segundo lugar, se describió un mecanismo común de activación de la respuesta protectora. En tercer lugar, se proporcionó una conexión entre la acumulación de daño en el ADN y la neurodegeneración. Finalmente, por medio de una metodología de análisis integrador sobre datos de transcriptómica de cerebro humano se encontró que en envejecimiento normal los astrocitos desarrollan dos fenotipos opuestos.
publishDate 2018
dc.date.created.none.fl_str_mv 2018-12-14
dc.date.issued.none.fl_str_mv 2018
dc.date.accessioned.none.fl_str_mv 2019-02-18T22:27:12Z
dc.date.available.none.fl_str_mv 2019-02-18T22:27:12Z
dc.type.eng.fl_str_mv doctoralThesis
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.document.spa.fl_str_mv Tesis
dc.type.spa.spa.fl_str_mv Tesis de doctorado
dc.identifier.doi.none.fl_str_mv https://doi.org/10.48713/10336_19101
dc.identifier.uri.none.fl_str_mv http://repository.urosario.edu.co/handle/10336/19101
url https://doi.org/10.48713/10336_19101
http://repository.urosario.edu.co/handle/10336/19101
dc.language.iso.none.fl_str_mv spa
language spa
dc.rights.spa.fl_str_mv Atribución-NoComercial-SinDerivadas 2.5 Colombia
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv Abierto (Texto Completo)
dc.rights.uri.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 2.5 Colombia
Abierto (Texto Completo)
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad del Rosario
dc.publisher.department.spa.fl_str_mv Facultad de Ciencias Naturales y Matemáticas
dc.publisher.program.spa.fl_str_mv Doctorado en Ciencias Biomédicas
institution Universidad del Rosario
dc.source.bibliographicCitation.spa.fl_str_mv Mendonca GV, Pezarat-Correia P, Vaz JR, Silva L, Heffernan KS. Impact of Aging on Endurance and Neuromuscular Physical Performance: The Role of Vascular Senescence. Sports Med. 2017;47(4):583-98.
Vermeij WP, Hoeijmakers JH, Pothof J. Aging: not all DNA damage is equal. Curr Opin Genet Dev. 2014;26:124-30.
Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361(15):1475-85.
Brown-Borg HM. Longevity in mice: is stress resistance a common factor? Age (Dordr). 2006;28(2):145-62
Mitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, et al. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell. 2010;9(1):40-53.
Susa D, Mitchell JR, Verweij M, van de Ven M, Roest H, van den Engel S, et al. Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in mice. Aging Cell. 2009;8(2):192-200
Schumacher B, van der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y, et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 2008;4(8):e1000161
Cole JH, Franke K. Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers. Trends Neurosci. 2017;40(12):681-90
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217
Bjorksten J, Tenhu H. The crosslinking theory of aging--added evidence. Exp Gerontol. 1990;25(2):91-5
Afanas'ev I. Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory, Hormesis, and TOR. Aging Dis. 2010;1(2):75-88
Wei W, Ji S. Cellular senescence: Molecular mechanisms and pathogenicity. J Cell Physiol. 2018;233(12):9121-35
Roche Y, Zhang D, Segers-Nolten GM, Vermeulen W, Wyman C, Sugasawa K, et al. Fluorescence correlation spectroscopy of the binding of nucleotide excision repair protein XPC-hHr23B with DNA substrates. J Fluoresc. 2008;18(5):987-95
Mitchell JR, Hoeijmakers JH, Niedernhofer LJ. Divide and conquer: nucleotide excision repair battles cancer and ageing. Curr Opin Cell Biol. 2003;15(2):232-40
Diderich KE, Nicolaije C, Priemel M, Waarsing JH, Day JS, Brandt RM, et al. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice. Age (Dordr). 2012;34(4):845-61
Nagtegaal AP, Rainey RN, van der Pluijm I, Brandt RM, van der Horst GT, Borst JG, et al. Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice. J Neurosci. 2015;35(10):4280-6
Jaarsma D, van der Pluijm I, van der Horst GT, Hoeijmakers JH. Cockayne syndrome pathogenesis: lessons from mouse models. Mech Ageing Dev. 2013;134(5-6):180-95
van der Pluijm I, Garinis GA, Brandt RM, Gorgels TG, Wijnhoven SW, Diderich KE, et al. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol. 2007;5(1):e2
Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006;444(7122):1038-43.
Spoor M, Nagtegaal AP, Ridwan Y, Borgesius NZ, van Alphen B, van der Pluijm I, et al. Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(δ/-) mouse. Mech Ageing Dev. 2012;133(2-3):59-67
Vo N, Seo HY, Robinson A, Sowa G, Bentley D, Taylor L, et al. Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res. 2010;28(12):1600-7
Schermer B, Bartels V, Frommolt P, Habermann B, Braun F, Schultze JL, et al. Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging. BMC Genomics. 2013;14:559
Garinis GA, Uittenboogaard LM, Stachelscheid H, Fousteri M, van Ijcken W, Breit TM, et al. Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nat Cell Biol. 2009;11(5):604-15
Madabhushi R, Pan L, Tsai LH. DNA damage and its links to neurodegeneration. Neuron. 2014;83(2):266-82
Martin LJ. DNA damage and repair: relevance to mechanisms of neurodegeneration. J Neuropathol Exp Neurol. 2008;67(5):377-87
Sepe S, Payan-Gomez C, Milanese C, Hoeijmakers JH, Mastroberardino PG. Nucleotide excision repair in chronic neurodegenerative diseases. DNA Repair (Amst). 2013;12(8):568-77
Borgesius NZ, de Waard MC, van der Pluijm I, Omrani A, Zondag GC, van der Horst GT, et al. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci. 2011;31(35):12543-53
Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature. 1988;334(6180):345-8
Ferrante RJ, Kowall NW, Beal MF, Richardson EP, Bird ED, Martin JB. Selective sparing of a class of striatal neurons in Huntington's disease. Science. 1985;230(4725):561-3
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112(4):389-404.
Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010;328(5976):321-6.
Fontana L, Nehme J, Demaria M. Caloric restriction and cellular senescence. Mech Ageing Dev. 2018;176:19-23.
López-Lluch G, Navas P. Calorie restriction as an intervention in ageing. J Physiol. 2016;594(8):2043-60.
Omodei D, Licastro D, Salvatore F, Crosby SD, Fontana L. Serum from humans on long-term calorie restriction enhances stress resistance in cell culture. Aging (Albany NY). 2013;5(8):599-606. 35. Huisman SA, de Bruijn P, Ghobadi Moghaddam-Helmantel IM, IJzermans JN, Wiemer EA, Mathijssen RH, et al. Fasting protects against the side effects of irinotecan treatment but does not affect anti-tumour activity in mice. Br J Pharmacol. 2016;173(5):804-14
Antoine DJ, Williams DP, Kipar A, Laverty H, Park BK. Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity. Mol Med. 2010;16(11-12):479-90
Verweij M, van de Ven M, Mitchell JR, van den Engel S, Hoeijmakers JH, Ijzermans JN, et al. Glucose supplementation does not interfere with fasting-induced protection against renal ischemia/reperfusion injury in mice. Transplantation. 2011;92(7):752-8
Isenberg JS, Roberts DD. The role of CD47 in pathogenesis and treatment of renal ischemia reperfusion injury. Pediatr Nephrol. 2018
Situmorang GR, Sheerin NS. Ischaemia reperfusion injury: mechanisms of progression to chronic graft dysfunction. Pediatr Nephrol. 2018.
Kezić A, Stajic N, Thaiss F. Innate Immune Response in Kidney Ischemia/Reperfusion Injury: Potential Target for Therapy. J Immunol Res. 2017;2017:6305439.
Barin-Le Guellec C, Largeau B, Bon D, Marquet P, Hauet T. Ischemia/reperfusion-associated tubular cells injury in renal transplantation: Can metabolomics inform about mechanisms and help identify new therapeutic targets? Pharmacol Res. 2018;129:34-43
Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121(11):4210-21
Jongbloed F, de Bruin RW, Pennings JL, Payán-Gómez C, van den Engel S, van Oostrom CT, et al. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice. PLoS One. 2014;9(6):e100853
Jongbloed F, Saat TC, Verweij M, Payan-Gomez C, Hoeijmakers JH, van den Engel S, et al. A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction. Sci Rep. 2017;7:40901
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412. 46. Ringnér M. What is principal component analysis? Nat Biotechnol. 2008;26(3):303-4
Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115-21
Xia J, Fjell CD, Mayer ML, Pena OM, Wishart DS, Hancock RE. INMEX--a web-based tool for integrative meta-analysis of expression data. Nucleic Acids Res. 2013;41(Web Server issue):W63-70
Sinclair DA. Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev. 2005;126(9):987-1002
Estrela GR, Wasinski F, Batista RO, Hiyane MI, Felizardo RJ, Cunha F, et al. Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation. Front Physiol. 2017;8:116
Martinez-Jimenez CP, Eling N, Chen HC, Vallejos CA, Kolodziejczyk AA, Connor F, et al. Aging increases cell-to-cell transcriptional variability upon immune stimulation. Science. 2017;355(6332):1433-6
Enge M, Arda HE, Mignardi M, Beausang J, Bottino R, Kim SK, et al. Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns. Cell. 2017;171(2):321-30.e14
Ein-Dor L, Zuk O, Domany E. Thousands of samples are needed to generate a robust gene list for predicting outcome in cancer. Proc Natl Acad Sci U S A. 2006;103(15):5923-8
Hong G, Zhang W, Li H, Shen X, Guo Z. Separate enrichment analysis of pathways for up- and downregulated genes. J R Soc Interface. 2014;11(92):20130950
Goldstein JL, Zhao TJ, Li RL, Sherbet DP, Liang G, Brown MS. Surviving starvation: essential role of the ghrelin-growth hormone axis. Cold Spring Harb Symp Quant Biol. 2011;76:121-7. 56. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-92
Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: insights from animal models. Food Chem Toxicol. 2013;60:38-44
Lou Z, Wang AP, Duan XM, Hu GH, Song GL, Zuo ML, et al. Upregulation of NOX2 and NOX4 Mediated by TGF-β Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury. Cell Physiol Biochem. 2018;46(5):2103-13
Martinez BA, Petersen DA, Gaeta AL, Stanley SP, Caldwell GA, Caldwell KA. Dysregulation of the Mitochondrial Unfolded Protein Response Induces Non-Apoptotic Dopaminergic Neurodegeneration in. J Neurosci. 2017;37(46):11085-100
Olivera-Perez HM, Lam L, Dang J, Jiang W, Rodriguez F, Rigali E, et al. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment. FASEB J. 2017;31(10):4359-69
Peng W, Robertson L, Gallinetti J, Mejia P, Vose S, Charlip A, et al. Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. Sci Transl Med. 2012;4(118):118ra11. 62. Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell. 2015;14(4):497-510
Masoro EJ. Caloric restriction and aging: controversial issues. J Gerontol A Biol Sci Med Sci. 2006;61(1):14-9
Dang W. The controversial world of sirtuins. Drug Discov Today Technol. 2014;12:e9-e17
Meijer AJ, Lorin S, Blommaart EF, Codogno P. Regulation of autophagy by amino acids and MTOR-dependent signal transduction. Amino Acids. 2015;47(10):2037-63
Valente E, Rocha M. Integrating data from heterogeneous DNA microarray platforms. J Integr Bioinform. 2015;12(4):281
McCall MN, Jaffee HA, Irizarry RA. fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays. Bioinformatics. 2012;28(23):3153-4
Carty CL, Kooperberg C, Neuhouser ML, Tinker L, Howard B, Wactawski-Wende J, et al. Low-fat dietary pattern and change in body-composition traits in the Women's Health Initiative Dietary Modification Trial. Am J Clin Nutr. 2011;93(3):516-24
Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295(6):643-54
Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295(6):629-42
Huang dW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1-13. 72. Tseng GC, Ghosh D, Feingold E. Comprehensive literature review and statistical considerations for microarray meta-analysis. Nucleic Acids Res. 2012;40(9):3785-99
Seo J, Gordish-Dressman H, Hoffman EP. An interactive power analysis tool for microarray hypothesis testing and generation. Bioinformatics. 2006;22(7):808-14
Lee SE, Koo YD, Lee JS, Kwak SH, Jung HS, Cho YM, et al. Retinoid X receptor α overexpression alleviates mitochondrial dysfunction-induced insulin resistance through transcriptional regulation of insulin receptor substrate 1. Mol Cells. 2015;38(4):356-61
Amigo I, Kowaltowski AJ. Dietary restriction in cerebral bioenergetics and redox state. Redox Biol. 2014;2:296-304
Choi BK, Kim JH, Jung JS, Lee YS, Han ME, Baek SY, et al. Reduction of ischemia-induced cerebral injury by all-trans-retinoic acid. Exp Brain Res. 2009;193(4):581-9
Shen H, Luo Y, Kuo CC, Deng X, Chang CF, Harvey BK, et al. 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein. J Neurosci Res. 2009;87(2):545-55
Fusco S, Pani G. Brain response to calorie restriction. Cell Mol Life Sci. 2013;70(17):3157-70
Ali AH, Carey EJ, Lindor KD. Recent advances in the development of farnesoid X receptor agonists. Ann Transl Med. 2015;3(1):5
Mellon I. Transcription-coupled repair: a complex affair. Mutat Res. 2005;577(1-2):155-61
Jaarsma D, van der Pluijm I, de Waard MC, Haasdijk ED, Brandt R, Vermeij M, et al. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet. 2011;7(12):e1002405
Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience. 2007;145(4):1388-96
DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, et al. Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol. 2008;65(8):1074-80
Sepe S, Milanese C, Gabriels S, Derks KW, Payan-Gomez C, van IJcken WF, et al. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease. Cell Rep. 2016;15(9):1866-75
Ahmad A, Robinson AR, Duensing A, van Drunen E, Beverloo HB, Weisberg DB, et al. ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol Cell Biol. 2008;28(16):5082-92
Brouwer RW, van den Hout MC, Grosveld FG, van Ijcken WF. NARWHAL, a primary analysis pipeline for NGS data. Bioinformatics. 2012;28(2):284-5
Xu G, Deng N, Zhao Z, Judeh T, Flemington E, Zhu D. SAMMate: a GUI tool for processing short read alignments in SAM/BAM format. Source Code Biol Med. 2011;6(1):2
Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, et al. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med. 2010;2(52):52ra73
Xiao Y, Hsiao TH, Suresh U, Chen HI, Wu X, Wolf SE, et al. A novel significance score for gene selection and ranking. Bioinformatics. 2014;30(6):801-7
Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007;23(23):3251-3
Vivar JC, Pemu P, McPherson R, Ghosh S. Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology. OMICS. 2013;17(8):414-22
Mutez E, Nkiliza A, Belarbi K, de Broucker A, Vanbesien-Mailliot C, Bleuse S, et al. Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease. Neurobiol Dis. 2014;63:165-70
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-73
Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10:48
Milanese C, Cerri S, Ulusoy A, Gornati SV, Plat A, Gabriels S, et al. Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease. Cell Death Dis. 2018;9(8):818
Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, et al. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature. 2016;537(7620):427-31
Caspers S, Moebus S, Lux S, Pundt N, Schütz H, Mühleisen TW, et al. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS. Front Aging Neurosci. 2014;6:149
Lemaitre H, Goldman AL, Sambataro F, Verchinski BA, Meyer-Lindenberg A, Weinberger DR, et al. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging. 2012;33(3):617.e1-9
larke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA. Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A. 2018;115(8):E1896-E905
Chen CY, Logan RW, Ma T, Lewis DA, Tseng GC, Sibille E, et al. Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci U S A. 2016;113(1):206-11
Rhinn H, Abeliovich A. Differential Aging Analysis in Human Cerebral Cortex Identifies Variants in TMEM106B and GRN that Regulate Aging Phenotypes. Cell Syst. 2017;4(4):404-15.e5
de Magalhães JP, Curado J, Church GM. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics. 2009;25(7):875-81
Dillman AA, Majounie E, Ding J, Gibbs JR, Hernandez D, Arepalli S, et al. Transcriptomic profiling of the human brain reveals that altered synaptic gene expression is associated with chronological aging. Sci Rep. 2017;7(1):16890
Eijssen LM, Jaillard M, Adriaens ME, Gaj S, de Groot PJ, Müller M, et al. User-friendly solutions for microarray quality control and pre-processing on ArrayAnalysis.org. Nucleic Acids Res. 2013;41(Web Server issue):W71-6
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47
Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118-27
Wang X, Kang DD, Shen K, Song C, Lu S, Chang LC, et al. An R package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection. Bioinformatics. 2012;28(19):2534-6
Rhodes DR, Barrette TR, Rubin MA, Ghosh D, Chinnaiyan AM. Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. Cancer Res. 2002;62(15):4427-33
Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41(Web Server issue):W77-83
Lanz TA, Joshi JJ, Reinhart V, Johnson K, Grantham LE, Volfson D. STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder. PLoS One. 2015;10(3):e0121744
Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, et al. Transcriptional neoteny in the human brain. Proc Natl Acad Sci U S A. 2009;106(14):5743-8
Maycox PR, Kelly F, Taylor A, Bates S, Reid J, Logendra R, et al. Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Mol Psychiatry. 2009;14(12):1083-94
Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 2010;20(9):1207-18
Walsh CJ, Hu P, Batt J, Santos CC. Microarray Meta-Analysis and Cross-Platform Normalization: Integrative Genomics for Robust Biomarker Discovery. Microarrays (Basel). 2015;4(3):389-406
Heberle H, Meirelles GV, da Silva FR, Telles GP, Minghim R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 2015;16:169
Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008;28(1):264-78
Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. J Neurosci. 2012;32(18):6391-410
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481-7
Astarita G, Avanesian A, Grimaldi B, Realini N, Justinova Z, Panlilio LV, et al. Methamphetamine accelerates cellular senescence through stimulation of de novo ceramide biosynthesis. PLoS One. 2015;10(2):e0116961
Bortell N, Basova L, Semenova S, Fox HS, Ravasi T, Marcondes MC. Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. J Neuroinflammation. 2017;14(1):49
Ugbode CI, Smith I, Whalley BJ, Hirst WD, Rattray M. Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection. J Neurochem. 2017;142(3):429-43
Pujato M, Kieken F, Skiles AA, Tapinos N, Fiser A. Prediction of DNA binding motifs from 3D models of transcription factors; identifying TLX3 regulated genes. Nucleic Acids Res. 2014;42(22):13500-12
Lee JS, Ward WO, Ren H, Vallanat B, Darlington GJ, Han ES, et al. Meta-analysis of gene expression in the mouse liver reveals biomarkers associated with inflammation increased early during aging. Mech Ageing Dev. 2012;133(7):467-78
Harris SE, Riggio V, Evenden L, Gilchrist T, McCafferty S, Murphy L, et al. Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936. Aging (Albany NY). 2017;9(12):2489-503
Bryois J, Buil A, Ferreira PG, Panousis NI, Brown AA, Viñuela A, et al. Time-dependent genetic effects on gene expression implicate aging processes. Genome Res. 2017;27(4):545-52
Reynolds LM, Ding J, Taylor JR, Lohman K, Soranzo N, de la Fuente A, et al. Transcriptomic profiles of aging in purified human immune cells. BMC Genomics. 2015;16:333
Voutetakis K, Chatziioannou A, Gonos ES, Trougakos IP. Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence and In Vivo Tissue Ageing. Oxid Med Cell Longev. 2015;2015:732914
Stranahan AM, Jiam NT, Spiegel AM, Gallagher M. Aging reduces total neuron number in the dorsal component of the rodent prefrontal cortex. J Comp Neurol. 2012;520(6):1318-26
Wellman CL, Sengelaub DR. Alterations in dendritic morphology of frontal cortical neurons after basal forebrain lesions in adult and aged rats. Brain Res. 1995;669(1):48-58
Diaz F, Villena A, Gonzalez P, Requena V, Rius F, Perez De Vargas I. Stereological age-related changes in neurons of the rat dorsal lateral geniculate nucleus. Anat Rec. 1999;255(4):396-400
Morterá P, Herculano-Houzel S. Age-related neuronal loss in the rat brain starts at the end of adolescence. Front Neuroanat. 2012;6:45
Di Lorenzo Alho AT, Suemoto CK, Polichiso L, Tampellini E, de Oliveira KC, Molina M, et al. Three-dimensional and stereological characterization of the human substantia nigra during aging. Brain Struct Funct. 2016;221(7):3393-403
Mortazavi F, Wang X, Rosene DL, Rockland KS. White Matter Neurons in Young Adult and Aged Rhesus Monkey. Front Neuroanat. 2016;10:15
Mohan A, Thalamuthu A, Mather KA, Zhang Y, Catts VS, Weickert CS, et al. Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex. Neurobiol Aging. 2018;70:194-202
Farhy-Tselnicker I, van Casteren ACM, Lee A, Chang VT, Aricescu AR, Allen NJ. Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation. Neuron. 2017;96(2):428-45.e13
Kucukdereli H, Allen NJ, Lee AT, Feng A, Ozlu MI, Conatser LM, et al. Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc Natl Acad Sci U S A. 2011;108(32):E440-9
Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron. 1996;16(3):675-86
Fabricius K, Jacobsen JS, Pakkenberg B. Effect of age on neocortical brain cells in 90+ year old human females--a cell counting study. Neurobiol Aging. 2013;34(1):91-9
Walløe S, Pakkenberg B, Fabricius K. Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex. Front Hum Neurosci. 2014;8:508
Melo P, Magalhães A, Alves CJ, Tavares MA, de Sousa L, Summavielle T, et al. Methamphetamine mimics the neurochemical profile of aging in rats and impairs recognition memory. Neurotoxicology. 2012;33(3):491-9
Vašák M, Meloni G. Mammalian Metallothionein-3: New Functional and Structural Insights. Int J Mol Sci. 2017;18(6)
Chung RS, Adlard PA, Dittmann J, Vickers JC, Chuah MI, West AK. Neuron-glia communication: metallothionein expression is specifically up-regulated by astrocytes in response to neuronal injury. J Neurochem. 2004;88(2):454-61
West AK, Hidalgo J, Eddins D, Levin ED, Aschner M. Metallothionein in the central nervous system: Roles in protection, regeneration and cognition. Neurotoxicology. 2008;29(3):489-503
Swindell WR. Metallothionein and the biology of aging. Ageing Res Rev. 2011;10(1):132-45
Leung YK, Pankhurst M, Dunlop SA, Ray S, Dittmann J, Eaton ED, et al. Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways. Exp Neurol. 2010;221(1):98-106
Tanaka Y, Mizoguchi K. Influence of aging on chondroitin sulfate proteoglycan expression and neural stem/progenitor cells in rat brain and improving effects of a herbal medicine, yokukansan. Neuroscience. 2009;164(3):1224-34
Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 2010;11(4):276-87
Lavialle M, Aumann G, Anlauf E, Pröls F, Arpin M, Derouiche A. Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc Natl Acad Sci U S A. 2011;108(31):12915-9
Freymuth PS, Fitzsimons HL. The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila. Mol Brain. 2017;10(1):41
Persson A, Lindberg OR, Kuhn HG. Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo. Front Cell Neurosci. 2013;7:161
Moon Y, Kim JY, Kim WR, Kim HJ, Jang MJ, Nam Y, et al. Function of ezrin-radixin-moesin proteins in migration of subventricular zone-derived neuroblasts following traumatic brain injury. Stem Cells. 2013;31(8):1696-705
Matsui T, Yonemura S, Tsukita S. Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases. Curr Biol. 1999;9(21):1259-62
Shaw RJ, Henry M, Solomon F, Jacks T. RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/actin protrusions in fibroblasts. Mol Biol Cell. 1998;9(2):403-19
Yonemura S, Matsui T, Tsukita S. Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo. J Cell Sci. 2002;115(Pt 12):2569-80
Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416-29
Farmer WT, Abrahamsson T, Chierzi S, Lui C, Zaelzer C, Jones EV, et al. Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling. Science. 2016;351(6275):849-54
Chechneva OV, Deng W. Empowering sonic hedgehog to rescue brain cells after ischemic stroke. Neural Regen Res. 2015;10(3):360-2
Chechneva OV, Deng W. Empowering sonic hedgehog to rescue brain cells after ischemic stroke. Neural Regen Res. 2015;10(3):360-2
Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science. 2014;346(6205):89-93
Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature. 2013;497(7448):211-6
Payán-Gómez, C.; Rodríguez, D.; Amador-Muñoz, D.; Ramírez-Clavijo, S. Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex. Brain Sci. 2018, 8, 227
Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, et al. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation. 2012;9:151
Jongbloed F, de Bruin RW, Klaassen RA, Beekhof P, van Steeg H, Dor FJ, et al. Short-Term Preoperative Calorie and Protein Restriction Is Feasible in Healthy Kidney Donors and Morbidly Obese Patients Scheduled for Surgery. Nutrients. 2016;8(5)
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spelling Ramírez Clavijo, Sandra Rocío51866251600Payan-Gomez, CesarDoctor en Ciencias BiomédicasFull time763272336002019-02-18T22:27:12Z2019-02-18T22:27:12Z2018-12-142018El envejecimiento es la reducción de las capacidades fisiológicas y adaptativas del organismo con el paso del tiempo. La acumulación de daño en el ADN podría ser el evento central desencadenante del proceso de envejecimiento. Los síndromes progeroides causados por una deficiencia de la sub-vía de reparación de escisión de nucleótidos acoplada a transcripción (TCR-NER) presentan un vínculo directo entre daño en el ADN y envejecimiento. Hay un paralelo entre la respuesta transcripcional de ratones progeroides y ratones sometidos a restricción dietética (DR) (una intervención que prolonga la vida). La DR aumenta la resistencia a diferentes formas de estrés. Ratones deficientes en TCR-NER también son menos susceptibles a un tipo de estrés agudo. El paralelo entre las respuestas transcriptómicas de los animales en dos extremos de esperanza de vida se ha explicado por la existencia de una respuesta de supervivencia programada. Esta tesis aborda varias cuestiones relacionadas con la respuesta de supervivencia utilizando principalmente el análisis de datos transcriptómicos. Primero, se estableció que los ratones viejos activan una respuesta de supervivencia incompleta después de tres días de DR, en segundo lugar, se describió un mecanismo común de activación de la respuesta protectora. En tercer lugar, se proporcionó una conexión entre la acumulación de daño en el ADN y la neurodegeneración. Finalmente, por medio de una metodología de análisis integrador sobre datos de transcriptómica de cerebro humano se encontró que en envejecimiento normal los astrocitos desarrollan dos fenotipos opuestos.Aging is defined as the reduction in the physiological and adaptive capabilities of organisms with the passage of time. The accumulation of DNA damage could be the central event on which other factors related to the aging process coalesce. One of the links connecting DNA damage to aging are the progeroid syndromes caused by a deficiency of DNA transcription-coupled nucleotide excision repair (TCR-NER) subpathway. There is a parallel between the transcriptional response of progeroid mice and mice on a dietary restriction (DR) regimen (an intervention that extend the lifespan). DR increased resistance to different forms of acute stress. Corroborating that TCR-NER deficiency induces activation of similar protective mechanisms, Csb-/- and Csa-/- mice are less susceptible to renal ischemia-reperfusion injury. The parallel between the transcriptomic responses of animals at two life expectancy extremes, in addition to the shared increase in resistance to ischemia-reperfusion injury, has been explained by the existence of a programmed survival response. This thesis addresses several questions related with the survival response, the mechanism of neurodegeneration and normal aging using mainly analysis of transcriptomic data. First, it was established that old mice activate an incomplete survival response after three days of DR, second, a common mechanism of activation of the protective response was described. Third, a connection between the accumulation of DNA damage and neurodegeneration was provided. Finally, an integrative methodology of analysis was used over brain human transcriptomic data, the result was the identification of an opposite activation of astrocytes in the human aged prefrontal cortex.application/pdfhttps://doi.org/10.48713/10336_19101 http://repository.urosario.edu.co/handle/10336/19101spaUniversidad del RosarioFacultad de Ciencias Naturales y MatemáticasDoctorado en Ciencias BiomédicasAtribución-NoComercial-SinDerivadas 2.5 ColombiaAbierto (Texto Completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.http://creativecommons.org/licenses/by-nc-nd/2.5/co/http://purl.org/coar/access_right/c_abf2Mendonca GV, Pezarat-Correia P, Vaz JR, Silva L, Heffernan KS. Impact of Aging on Endurance and Neuromuscular Physical Performance: The Role of Vascular Senescence. Sports Med. 2017;47(4):583-98.Vermeij WP, Hoeijmakers JH, Pothof J. Aging: not all DNA damage is equal. Curr Opin Genet Dev. 2014;26:124-30.Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361(15):1475-85.Brown-Borg HM. Longevity in mice: is stress resistance a common factor? Age (Dordr). 2006;28(2):145-62Mitchell JR, Verweij M, Brand K, van de Ven M, Goemaere N, van den Engel S, et al. Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. Aging Cell. 2010;9(1):40-53.Susa D, Mitchell JR, Verweij M, van de Ven M, Roest H, van den Engel S, et al. Congenital DNA repair deficiency results in protection against renal ischemia reperfusion injury in mice. Aging Cell. 2009;8(2):192-200Schumacher B, van der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y, et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 2008;4(8):e1000161Cole JH, Franke K. Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers. Trends Neurosci. 2017;40(12):681-90López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217Bjorksten J, Tenhu H. The crosslinking theory of aging--added evidence. Exp Gerontol. 1990;25(2):91-5Afanas'ev I. Signaling and Damaging Functions of Free Radicals in Aging-Free Radical Theory, Hormesis, and TOR. Aging Dis. 2010;1(2):75-88Wei W, Ji S. Cellular senescence: Molecular mechanisms and pathogenicity. J Cell Physiol. 2018;233(12):9121-35Roche Y, Zhang D, Segers-Nolten GM, Vermeulen W, Wyman C, Sugasawa K, et al. Fluorescence correlation spectroscopy of the binding of nucleotide excision repair protein XPC-hHr23B with DNA substrates. J Fluoresc. 2008;18(5):987-95Mitchell JR, Hoeijmakers JH, Niedernhofer LJ. Divide and conquer: nucleotide excision repair battles cancer and ageing. Curr Opin Cell Biol. 2003;15(2):232-40Diderich KE, Nicolaije C, Priemel M, Waarsing JH, Day JS, Brandt RM, et al. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice. Age (Dordr). 2012;34(4):845-61Nagtegaal AP, Rainey RN, van der Pluijm I, Brandt RM, van der Horst GT, Borst JG, et al. Cockayne syndrome group B (Csb) and group a (Csa) deficiencies predispose to hearing loss and cochlear hair cell degeneration in mice. J Neurosci. 2015;35(10):4280-6Jaarsma D, van der Pluijm I, van der Horst GT, Hoeijmakers JH. Cockayne syndrome pathogenesis: lessons from mouse models. Mech Ageing Dev. 2013;134(5-6):180-95van der Pluijm I, Garinis GA, Brandt RM, Gorgels TG, Wijnhoven SW, Diderich KE, et al. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol. 2007;5(1):e2Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature. 2006;444(7122):1038-43.Spoor M, Nagtegaal AP, Ridwan Y, Borgesius NZ, van Alphen B, van der Pluijm I, et al. Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(δ/-) mouse. Mech Ageing Dev. 2012;133(2-3):59-67Vo N, Seo HY, Robinson A, Sowa G, Bentley D, Taylor L, et al. Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res. 2010;28(12):1600-7Schermer B, Bartels V, Frommolt P, Habermann B, Braun F, Schultze JL, et al. Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging. BMC Genomics. 2013;14:559Garinis GA, Uittenboogaard LM, Stachelscheid H, Fousteri M, van Ijcken W, Breit TM, et al. Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity. Nat Cell Biol. 2009;11(5):604-15Madabhushi R, Pan L, Tsai LH. DNA damage and its links to neurodegeneration. Neuron. 2014;83(2):266-82Martin LJ. DNA damage and repair: relevance to mechanisms of neurodegeneration. J Neuropathol Exp Neurol. 2008;67(5):377-87Sepe S, Payan-Gomez C, Milanese C, Hoeijmakers JH, Mastroberardino PG. Nucleotide excision repair in chronic neurodegenerative diseases. DNA Repair (Amst). 2013;12(8):568-77Borgesius NZ, de Waard MC, van der Pluijm I, Omrani A, Zondag GC, van der Horst GT, et al. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci. 2011;31(35):12543-53Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature. 1988;334(6180):345-8Ferrante RJ, Kowall NW, Beal MF, Richardson EP, Bird ED, Martin JB. Selective sparing of a class of striatal neurons in Huntington's disease. Science. 1985;230(4725):561-3Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112(4):389-404.Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010;328(5976):321-6.Fontana L, Nehme J, Demaria M. Caloric restriction and cellular senescence. Mech Ageing Dev. 2018;176:19-23.López-Lluch G, Navas P. Calorie restriction as an intervention in ageing. J Physiol. 2016;594(8):2043-60.Omodei D, Licastro D, Salvatore F, Crosby SD, Fontana L. Serum from humans on long-term calorie restriction enhances stress resistance in cell culture. Aging (Albany NY). 2013;5(8):599-606. 35. Huisman SA, de Bruijn P, Ghobadi Moghaddam-Helmantel IM, IJzermans JN, Wiemer EA, Mathijssen RH, et al. Fasting protects against the side effects of irinotecan treatment but does not affect anti-tumour activity in mice. Br J Pharmacol. 2016;173(5):804-14Antoine DJ, Williams DP, Kipar A, Laverty H, Park BK. Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity. Mol Med. 2010;16(11-12):479-90Verweij M, van de Ven M, Mitchell JR, van den Engel S, Hoeijmakers JH, Ijzermans JN, et al. Glucose supplementation does not interfere with fasting-induced protection against renal ischemia/reperfusion injury in mice. Transplantation. 2011;92(7):752-8Isenberg JS, Roberts DD. The role of CD47 in pathogenesis and treatment of renal ischemia reperfusion injury. Pediatr Nephrol. 2018Situmorang GR, Sheerin NS. Ischaemia reperfusion injury: mechanisms of progression to chronic graft dysfunction. Pediatr Nephrol. 2018.Kezić A, Stajic N, Thaiss F. Innate Immune Response in Kidney Ischemia/Reperfusion Injury: Potential Target for Therapy. J Immunol Res. 2017;2017:6305439.Barin-Le Guellec C, Largeau B, Bon D, Marquet P, Hauet T. Ischemia/reperfusion-associated tubular cells injury in renal transplantation: Can metabolomics inform about mechanisms and help identify new therapeutic targets? Pharmacol Res. 2018;129:34-43Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 2011;121(11):4210-21Jongbloed F, de Bruin RW, Pennings JL, Payán-Gómez C, van den Engel S, van Oostrom CT, et al. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice. PLoS One. 2014;9(6):e100853Jongbloed F, Saat TC, Verweij M, Payan-Gomez C, Hoeijmakers JH, van den Engel S, et al. A signature of renal stress resistance induced by short-term dietary restriction, fasting, and protein restriction. Sci Rep. 2017;7:40901Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412. 46. Ringnér M. What is principal component analysis? Nat Biotechnol. 2008;26(3):303-4Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115-21Xia J, Fjell CD, Mayer ML, Pena OM, Wishart DS, Hancock RE. INMEX--a web-based tool for integrative meta-analysis of expression data. Nucleic Acids Res. 2013;41(Web Server issue):W63-70Sinclair DA. Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev. 2005;126(9):987-1002Estrela GR, Wasinski F, Batista RO, Hiyane MI, Felizardo RJ, Cunha F, et al. Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation. Front Physiol. 2017;8:116Martinez-Jimenez CP, Eling N, Chen HC, Vallejos CA, Kolodziejczyk AA, Connor F, et al. Aging increases cell-to-cell transcriptional variability upon immune stimulation. Science. 2017;355(6332):1433-6Enge M, Arda HE, Mignardi M, Beausang J, Bottino R, Kim SK, et al. Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns. Cell. 2017;171(2):321-30.e14Ein-Dor L, Zuk O, Domany E. Thousands of samples are needed to generate a robust gene list for predicting outcome in cancer. Proc Natl Acad Sci U S A. 2006;103(15):5923-8Hong G, Zhang W, Li H, Shen X, Guo Z. Separate enrichment analysis of pathways for up- and downregulated genes. J R Soc Interface. 2014;11(92):20130950Goldstein JL, Zhao TJ, Li RL, Sherbet DP, Liang G, Brown MS. Surviving starvation: essential role of the ghrelin-growth hormone axis. Cold Spring Harb Symp Quant Biol. 2011;76:121-7. 56. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-92Chen Y, Dong H, Thompson DC, Shertzer HG, Nebert DW, Vasiliou V. Glutathione defense mechanism in liver injury: insights from animal models. Food Chem Toxicol. 2013;60:38-44Lou Z, Wang AP, Duan XM, Hu GH, Song GL, Zuo ML, et al. Upregulation of NOX2 and NOX4 Mediated by TGF-β Signaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury. Cell Physiol Biochem. 2018;46(5):2103-13Martinez BA, Petersen DA, Gaeta AL, Stanley SP, Caldwell GA, Caldwell KA. Dysregulation of the Mitochondrial Unfolded Protein Response Induces Non-Apoptotic Dopaminergic Neurodegeneration in. J Neurosci. 2017;37(46):11085-100Olivera-Perez HM, Lam L, Dang J, Jiang W, Rodriguez F, Rigali E, et al. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment. FASEB J. 2017;31(10):4359-69Peng W, Robertson L, Gallinetti J, Mejia P, Vose S, Charlip A, et al. Surgical stress resistance induced by single amino acid deprivation requires Gcn2 in mice. Sci Transl Med. 2012;4(118):118ra11. 62. Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell. 2015;14(4):497-510Masoro EJ. Caloric restriction and aging: controversial issues. J Gerontol A Biol Sci Med Sci. 2006;61(1):14-9Dang W. The controversial world of sirtuins. Drug Discov Today Technol. 2014;12:e9-e17Meijer AJ, Lorin S, Blommaart EF, Codogno P. Regulation of autophagy by amino acids and MTOR-dependent signal transduction. Amino Acids. 2015;47(10):2037-63Valente E, Rocha M. Integrating data from heterogeneous DNA microarray platforms. J Integr Bioinform. 2015;12(4):281McCall MN, Jaffee HA, Irizarry RA. fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays. Bioinformatics. 2012;28(23):3153-4Carty CL, Kooperberg C, Neuhouser ML, Tinker L, Howard B, Wactawski-Wende J, et al. Low-fat dietary pattern and change in body-composition traits in the Women's Health Initiative Dietary Modification Trial. Am J Clin Nutr. 2011;93(3):516-24Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, et al. Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295(6):643-54Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al. Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006;295(6):629-42Huang dW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1-13. 72. Tseng GC, Ghosh D, Feingold E. Comprehensive literature review and statistical considerations for microarray meta-analysis. Nucleic Acids Res. 2012;40(9):3785-99Seo J, Gordish-Dressman H, Hoffman EP. An interactive power analysis tool for microarray hypothesis testing and generation. Bioinformatics. 2006;22(7):808-14Lee SE, Koo YD, Lee JS, Kwak SH, Jung HS, Cho YM, et al. Retinoid X receptor α overexpression alleviates mitochondrial dysfunction-induced insulin resistance through transcriptional regulation of insulin receptor substrate 1. Mol Cells. 2015;38(4):356-61Amigo I, Kowaltowski AJ. Dietary restriction in cerebral bioenergetics and redox state. Redox Biol. 2014;2:296-304Choi BK, Kim JH, Jung JS, Lee YS, Han ME, Baek SY, et al. Reduction of ischemia-induced cerebral injury by all-trans-retinoic acid. Exp Brain Res. 2009;193(4):581-9Shen H, Luo Y, Kuo CC, Deng X, Chang CF, Harvey BK, et al. 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein. J Neurosci Res. 2009;87(2):545-55Fusco S, Pani G. Brain response to calorie restriction. Cell Mol Life Sci. 2013;70(17):3157-70Ali AH, Carey EJ, Lindor KD. Recent advances in the development of farnesoid X receptor agonists. Ann Transl Med. 2015;3(1):5Mellon I. Transcription-coupled repair: a complex affair. Mutat Res. 2005;577(1-2):155-61Jaarsma D, van der Pluijm I, de Waard MC, Haasdijk ED, Brandt R, Vermeij M, et al. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet. 2011;7(12):e1002405Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience. 2007;145(4):1388-96DelleDonne A, Klos KJ, Fujishiro H, Ahmed Z, Parisi JE, Josephs KA, et al. Incidental Lewy body disease and preclinical Parkinson disease. Arch Neurol. 2008;65(8):1074-80Sepe S, Milanese C, Gabriels S, Derks KW, Payan-Gomez C, van IJcken WF, et al. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease. Cell Rep. 2016;15(9):1866-75Ahmad A, Robinson AR, Duensing A, van Drunen E, Beverloo HB, Weisberg DB, et al. ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol Cell Biol. 2008;28(16):5082-92Brouwer RW, van den Hout MC, Grosveld FG, van Ijcken WF. NARWHAL, a primary analysis pipeline for NGS data. Bioinformatics. 2012;28(2):284-5Xu G, Deng N, Zhao Z, Judeh T, Flemington E, Zhu D. SAMMate: a GUI tool for processing short read alignments in SAM/BAM format. Source Code Biol Med. 2011;6(1):2Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, et al. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med. 2010;2(52):52ra73Xiao Y, Hsiao TH, Suresh U, Chen HI, Wu X, Wolf SE, et al. A novel significance score for gene selection and ranking. Bioinformatics. 2014;30(6):801-7Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007;23(23):3251-3Vivar JC, Pemu P, McPherson R, Ghosh S. Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology. OMICS. 2013;17(8):414-22Mutez E, Nkiliza A, Belarbi K, de Broucker A, Vanbesien-Mailliot C, Bleuse S, et al. Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease. Neurobiol Dis. 2014;63:165-70Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-73Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10:48Milanese C, Cerri S, Ulusoy A, Gornati SV, Plat A, Gabriels S, et al. Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson's disease. Cell Death Dis. 2018;9(8):818Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, et al. Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature. 2016;537(7620):427-31Caspers S, Moebus S, Lux S, Pundt N, Schütz H, Mühleisen TW, et al. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS. Front Aging Neurosci. 2014;6:149Lemaitre H, Goldman AL, Sambataro F, Verchinski BA, Meyer-Lindenberg A, Weinberger DR, et al. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol Aging. 2012;33(3):617.e1-9larke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA. Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci U S A. 2018;115(8):E1896-E905Chen CY, Logan RW, Ma T, Lewis DA, Tseng GC, Sibille E, et al. Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci U S A. 2016;113(1):206-11Rhinn H, Abeliovich A. Differential Aging Analysis in Human Cerebral Cortex Identifies Variants in TMEM106B and GRN that Regulate Aging Phenotypes. Cell Syst. 2017;4(4):404-15.e5de Magalhães JP, Curado J, Church GM. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics. 2009;25(7):875-81Dillman AA, Majounie E, Ding J, Gibbs JR, Hernandez D, Arepalli S, et al. Transcriptomic profiling of the human brain reveals that altered synaptic gene expression is associated with chronological aging. Sci Rep. 2017;7(1):16890Eijssen LM, Jaillard M, Adriaens ME, Gaj S, de Groot PJ, Müller M, et al. User-friendly solutions for microarray quality control and pre-processing on ArrayAnalysis.org. Nucleic Acids Res. 2013;41(Web Server issue):W71-6Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118-27Wang X, Kang DD, Shen K, Song C, Lu S, Chang LC, et al. An R package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection. Bioinformatics. 2012;28(19):2534-6Rhodes DR, Barrette TR, Rubin MA, Ghosh D, Chinnaiyan AM. Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. Cancer Res. 2002;62(15):4427-33Wang J, Duncan D, Shi Z, Zhang B. WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41(Web Server issue):W77-83Lanz TA, Joshi JJ, Reinhart V, Johnson K, Grantham LE, Volfson D. STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder. PLoS One. 2015;10(3):e0121744Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, et al. Transcriptional neoteny in the human brain. Proc Natl Acad Sci U S A. 2009;106(14):5743-8Maycox PR, Kelly F, Taylor A, Bates S, Reid J, Logendra R, et al. Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Mol Psychiatry. 2009;14(12):1083-94Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 2010;20(9):1207-18Walsh CJ, Hu P, Batt J, Santos CC. Microarray Meta-Analysis and Cross-Platform Normalization: Integrative Genomics for Robust Biomarker Discovery. Microarrays (Basel). 2015;4(3):389-406Heberle H, Meirelles GV, da Silva FR, Telles GP, Minghim R. InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinformatics. 2015;16:169Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008;28(1):264-78Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. J Neurosci. 2012;32(18):6391-410Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481-7Astarita G, Avanesian A, Grimaldi B, Realini N, Justinova Z, Panlilio LV, et al. Methamphetamine accelerates cellular senescence through stimulation of de novo ceramide biosynthesis. PLoS One. 2015;10(2):e0116961Bortell N, Basova L, Semenova S, Fox HS, Ravasi T, Marcondes MC. Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. J Neuroinflammation. 2017;14(1):49Ugbode CI, Smith I, Whalley BJ, Hirst WD, Rattray M. Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection. J Neurochem. 2017;142(3):429-43Pujato M, Kieken F, Skiles AA, Tapinos N, Fiser A. Prediction of DNA binding motifs from 3D models of transcription factors; identifying TLX3 regulated genes. Nucleic Acids Res. 2014;42(22):13500-12Lee JS, Ward WO, Ren H, Vallanat B, Darlington GJ, Han ES, et al. Meta-analysis of gene expression in the mouse liver reveals biomarkers associated with inflammation increased early during aging. Mech Ageing Dev. 2012;133(7):467-78Harris SE, Riggio V, Evenden L, Gilchrist T, McCafferty S, Murphy L, et al. Age-related gene expression changes, and transcriptome wide association study of physical and cognitive aging traits, in the Lothian Birth Cohort 1936. Aging (Albany NY). 2017;9(12):2489-503Bryois J, Buil A, Ferreira PG, Panousis NI, Brown AA, Viñuela A, et al. Time-dependent genetic effects on gene expression implicate aging processes. Genome Res. 2017;27(4):545-52Reynolds LM, Ding J, Taylor JR, Lohman K, Soranzo N, de la Fuente A, et al. Transcriptomic profiles of aging in purified human immune cells. BMC Genomics. 2015;16:333Voutetakis K, Chatziioannou A, Gonos ES, Trougakos IP. Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence and In Vivo Tissue Ageing. Oxid Med Cell Longev. 2015;2015:732914Stranahan AM, Jiam NT, Spiegel AM, Gallagher M. Aging reduces total neuron number in the dorsal component of the rodent prefrontal cortex. J Comp Neurol. 2012;520(6):1318-26Wellman CL, Sengelaub DR. Alterations in dendritic morphology of frontal cortical neurons after basal forebrain lesions in adult and aged rats. Brain Res. 1995;669(1):48-58Diaz F, Villena A, Gonzalez P, Requena V, Rius F, Perez De Vargas I. Stereological age-related changes in neurons of the rat dorsal lateral geniculate nucleus. Anat Rec. 1999;255(4):396-400Morterá P, Herculano-Houzel S. Age-related neuronal loss in the rat brain starts at the end of adolescence. Front Neuroanat. 2012;6:45Di Lorenzo Alho AT, Suemoto CK, Polichiso L, Tampellini E, de Oliveira KC, Molina M, et al. Three-dimensional and stereological characterization of the human substantia nigra during aging. Brain Struct Funct. 2016;221(7):3393-403Mortazavi F, Wang X, Rosene DL, Rockland KS. White Matter Neurons in Young Adult and Aged Rhesus Monkey. Front Neuroanat. 2016;10:15Mohan A, Thalamuthu A, Mather KA, Zhang Y, Catts VS, Weickert CS, et al. Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex. Neurobiol Aging. 2018;70:194-202Farhy-Tselnicker I, van Casteren ACM, Lee A, Chang VT, Aricescu AR, Allen NJ. Astrocyte-Secreted Glypican 4 Regulates Release of Neuronal Pentraxin 1 from Axons to Induce Functional Synapse Formation. Neuron. 2017;96(2):428-45.e13Kucukdereli H, Allen NJ, Lee AT, Feng A, Ozlu MI, Conatser LM, et al. Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc Natl Acad Sci U S A. 2011;108(32):E440-9Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, et al. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron. 1996;16(3):675-86Fabricius K, Jacobsen JS, Pakkenberg B. Effect of age on neocortical brain cells in 90+ year old human females--a cell counting study. Neurobiol Aging. 2013;34(1):91-9Walløe S, Pakkenberg B, Fabricius K. Stereological estimation of total cell numbers in the human cerebral and cerebellar cortex. Front Hum Neurosci. 2014;8:508Melo P, Magalhães A, Alves CJ, Tavares MA, de Sousa L, Summavielle T, et al. Methamphetamine mimics the neurochemical profile of aging in rats and impairs recognition memory. Neurotoxicology. 2012;33(3):491-9Vašák M, Meloni G. Mammalian Metallothionein-3: New Functional and Structural Insights. Int J Mol Sci. 2017;18(6)Chung RS, Adlard PA, Dittmann J, Vickers JC, Chuah MI, West AK. Neuron-glia communication: metallothionein expression is specifically up-regulated by astrocytes in response to neuronal injury. J Neurochem. 2004;88(2):454-61West AK, Hidalgo J, Eddins D, Levin ED, Aschner M. Metallothionein in the central nervous system: Roles in protection, regeneration and cognition. Neurotoxicology. 2008;29(3):489-503Swindell WR. Metallothionein and the biology of aging. Ageing Res Rev. 2011;10(1):132-45Leung YK, Pankhurst M, Dunlop SA, Ray S, Dittmann J, Eaton ED, et al. Metallothionein induces a regenerative reactive astrocyte phenotype via JAK/STAT and RhoA signalling pathways. Exp Neurol. 2010;221(1):98-106Tanaka Y, Mizoguchi K. Influence of aging on chondroitin sulfate proteoglycan expression and neural stem/progenitor cells in rat brain and improving effects of a herbal medicine, yokukansan. Neuroscience. 2009;164(3):1224-34Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 2010;11(4):276-87Lavialle M, Aumann G, Anlauf E, Pröls F, Arpin M, Derouiche A. Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. Proc Natl Acad Sci U S A. 2011;108(31):12915-9Freymuth PS, Fitzsimons HL. The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila. Mol Brain. 2017;10(1):41Persson A, Lindberg OR, Kuhn HG. Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo. Front Cell Neurosci. 2013;7:161Moon Y, Kim JY, Kim WR, Kim HJ, Jang MJ, Nam Y, et al. Function of ezrin-radixin-moesin proteins in migration of subventricular zone-derived neuroblasts following traumatic brain injury. Stem Cells. 2013;31(8):1696-705Matsui T, Yonemura S, Tsukita S. Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases. Curr Biol. 1999;9(21):1259-62Shaw RJ, Henry M, Solomon F, Jacks T. RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/actin protrusions in fibroblasts. Mol Biol Cell. 1998;9(2):403-19Yonemura S, Matsui T, Tsukita S. Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin proteins: an essential role for polyphosphoinositides in vivo. J Cell Sci. 2002;115(Pt 12):2569-80Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416-29Farmer WT, Abrahamsson T, Chierzi S, Lui C, Zaelzer C, Jones EV, et al. Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling. Science. 2016;351(6275):849-54Chechneva OV, Deng W. Empowering sonic hedgehog to rescue brain cells after ischemic stroke. Neural Regen Res. 2015;10(3):360-2Chechneva OV, Deng W. Empowering sonic hedgehog to rescue brain cells after ischemic stroke. Neural Regen Res. 2015;10(3):360-2Baruch K, Deczkowska A, David E, Castellano JM, Miller O, Kertser A, et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science. 2014;346(6205):89-93Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature. 2013;497(7448):211-6Payán-Gómez, C.; Rodríguez, D.; Amador-Muñoz, D.; Ramírez-Clavijo, S. Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex. Brain Sci. 2018, 8, 227Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, et al. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation. 2012;9:151Jongbloed F, de Bruin RW, Klaassen RA, Beekhof P, van Steeg H, Dor FJ, et al. Short-Term Preoperative Calorie and Protein Restriction Is Feasible in Healthy Kidney Donors and Morbidly Obese Patients Scheduled for Surgery. 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