Download PDF
Open Access
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2018; 76(12): 831-839
DOI: 10.1590/0004-282X20180142
Article

Genes related to maintenance of autophagy and successful aging

Genes relacionados à manutenção da autofagia e envelhecimento bem-sucedido

Authors

  • Carolina Fioroto Chaves

    1   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brasil

  • Diego Robles Mazzotti

    1   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brasil

  • Maysa Seabra Cendoroglo

    2   Universidade Federal de São Paulo, Departamento de Medicina, São Paulo SP, Brasil

  • Luiz Roberto Ramos

    3   Universidade Federal de São Paulo, Departamento de Medicina Preventiva, São Paulo SP, Brasil

  • Sergio Tufik

    1   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brasil

  • Vanessa Cavalcante da Silva

    1   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brasil

  • Vânia D'Almeida

    1   Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo SP, Brasil
Further Information
Also available at
  Permissions and Reprints

ABSTRACT

Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

RESUMO

Considerando o envelhecimento como um fençmeno em que há um declínio nos processos essenciais a sobrevivência celular, investigamos as vias autofágica e proteassçmica em três grupos: jovens, idosos e longevos. O perfil de expressão dos genes relacionados à via autofágica foi analisado em sangue periférico, e a quantificação do proteassoma realizada em plasma. Não foram encontradas alterações significativas nas concentrações plasmáticas de proteassoma ou na correlação entre as concentrações de proteassoma e as idades. No entanto, alguns genes relacionados a autofagia e / ou apoptose foram expressos diferencialmente. Além disso, as análises de rede e de enriquecimento mostraram uma interação entre quatro dos cinco genes diferencialmente expressos e a associação desses ao processo transcricional. Considerando que os indivíduos longevos mantiveram tanto a expressão de genes ligados à maquinaria autofágica, quanto os níveis de proteassoma quando comparados aos idosos, concluímos que esses fatores poderiam ser considerados cruciais para o envelhecimento bem-sucedido.

Keywords:

Autophagy - longevity - gene expression - gene networks - proteasome endopeptidase complex

Palavras-chave:

Autofagia - longevidade - expressão gênica - redes regurladoras de genes - complexo de endopeptidases do proteassoma

Support

CNPq, CAPES, AFIP and FAPESP.CFC was a recipient of a CNPq scholarship. VCS is a recipient of a CAPES scholarship. VD'A is a recipient of a CNPq fellowship.




Publication History

Received: 02 July 2018

Accepted: 25 September 2018

Article published online:
22 August 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Troen BR. The biology of aging. Mt Sinai J Med. 2003 Jan;70(1):3-22.
  • 2 Korolchuk VI, Menzies FM, Rubinsztein DC. Mechanisms of cross-talk between the ubiquitin-proteasome and autophagylysosome systems. FEBS Lett. 2010 Apr;584(7):1393-8. https://doi.org/10.1016/j.febslet.2009.12.047
  • 3 Brooks P Fuertes G, Murray RZ, Bose S, Knecht E, Rechsteiner MC et al. Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem J. 2000 Feb;346(Pt 1):155-61. https://doi.org/10.1042/bj3460155
  • 4 Groll M, Bochtler M, Brandstetter H, Clausen T, Huber R. Molecular machines for protein degradation. ChemBioChem. 2005 Feb;6(2):222-56. https://doi.org/10.1002/cbic.200400313
  • 5 Nickell S, Beck F, Scheres SH, Korinek A, Forster F, Lasker K et al. Insights into the molecular architecture of the 26S proteasome. Proc Natl Acad Sci USA. 2009 Jul;106(29):11943-7. https://doi.org/10.1073/pnas.0905081106
  • 6 Ferrington DA, Husom AD, Thompson LV. Altered proteasome structure, function, and oxidation in aged muscle. FASEB J. 2005 Apr;19(6):644-6. https://doi.org/10.1096/fj.04-2578fje
  • 7 Petropoulos I, Conconi M, Wang X, Hoenel B, Brégégère F, Milner Y et al. Increase of oxidatively modified protein is associated with a decrease of proteasome activity and content in aging epidermal cells. J Gerontol A Biol Sci Med Sci. 2000 May;55(5):B220-7. https://doi.org/10.1093/gerona/55.5.B220
  • 8 Chondrogianni N, Petropoulos I, Franceschi C, Friguet B, Gonos ES. Fibroblast cultures from healthy centenarians have an active proteasome. Exp Gerontol. 2000 Sep;35(6-7):721-8. https://doi.org/10.1016/S0531-5565(00)00137-6
  • 9 Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science. 1999 Aug;285(5432):1390-3. https://doi.org/10.1126/science.285.5432.1390
  • 10 Wada M, Kosaka M, Saito S, Sano T, Tanaka K, Ichihara A. Serum concentration and localization in tumor cells of proteasomes in patients with hematologic malignancy and their pathophysiologic significance. J Lab Clin Med. 1993 Feb;121(2):215-23.
  • 11 Sixt SU, Dahlmann B. Extracellular, circulating proteasomes and ubiquitin - incidence and relevance. Biochim Biophys Acta. 2008 Dec;1782(12):817-23. https://doi.org/10.1016/j.bbadis.2008.06.005
  • 12 Zoeger A, Blau M, Egerer K, Feist E, Dahlmann B. Circulating proteasomes are functional and have a subtype pattern distinct from 20S proteasomes in major blood cells. Clin Chem. 2006 Nov;52(11):2079-86. https://doi.org/10.1373/clinchem.2006.072496
  • 13 Jakob C, Egerer K, Liebisch P Turkmen S, Zavrski I, Kuckelkorn U et al. Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma. Blood. 2007 Mar;109(5):2100-5. https://doi.org/10.1182/blood-2006-04-016360
  • 14 Stoebner PE, Lavabre-Bertrand T, Henry L, Guiraud I, Carillo S, Dandurand M et al. High plasma proteasome levels are detected in patients with metastatic malignant melanoma. Br J Dermatol. 2005 May;152(5):948-53. https://doi.org/10.1111/j.1365-2133.2005.06487.x
  • 15 Lavabre-Bertrand T, Henry L, Carillo S, Guiraud I, Ouali A, Dutaud D et al. Plasma proteasome level is a potential marker in patients with solid tumors and hemopoietic malignancies. Cancer. 2001 Nov;92(10):2493-500. https://doi.org/10.1002/1097-0142(20011115)92:10<2493::AID-CNCR1599>3.0.C0;2-F
  • 16 Roth GA, Moser B, Krenn C, Roth-Walter F, Hetz H, Richter S et al. Heightened levels of circulating 20S proteasome in critically ill patients. Eur J Clin Invest. 2005 Jun;35(6):399-403. https://doi.org/10.1111/j.1365-2362.2005.01508.x
  • 17 Huang J, Klionsky DJ. Autophagy and human disease. Cell Cycle. 2007 Aug;6(15):1837-49. https://doi.org/10.4161/cc.615.4511
  • 18 Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7. https://doi.org/10.1038/nrm2245
  • 19 Ramírez-Valle F, Braunstein S, Zavadil J, Formenti SC, Schneider RJ. eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy. J Cell Biol. 2008 Apr;181(2):293-307. https://doi.org/10.1083/jcb.200710215.
  • 20 Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010 Jul 1;38 Suppl:W214-20. https://doi.org/10.1093/nar/gkq537.
  • 21 Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013 Apr;14(1):128. https://doi.org/10.1186/1471-2105-14-128
  • 22 Terman A, Brunk UT. Myocyte aging and mitochondrial turnover. Exp Gerontol. 2004 May;39(5):701-5. https://doi.org/10.1016Zj.exger.2004.01.005
  • 23 Juhász G, Erdi B, Sass M, Neufeld TP. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev. 2007 Dec;21(23):3061-6. https://doi.org/10.1101/gad.1600707
  • 24 Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T et al. The role of autophagy during the early neonatal starvation period. Nature. 2004 Dec;432(7020):1032-6. https://doi.org/10.1038/nature03029
  • 25 Meléndez A, Tallóczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003 Sep;301(5638):1387-91. https://doi.org/10.1126/science.1087782
  • 26 Mariño G, Fernández AF, Cabrera S, Lundberg YW, Cabanillas R, Rodríguez F et al. Autophagy is essential for mouse sense of balance. J Clin Invest. 2010 Jul;120(7):2331-44. https://doi.org/10.1172/JCI42601
  • 27 Christensen KE, Wu Q, Wang X, Deng L, Caudill MA, Rozen R. Steatosis in mice is associated with gender, folate intake, and expression of genes of one-carbon metabolism. J Nutr. 2010 0ct;140(10):1736-41. https://doi.org/10.3945/jn.110.124917
  • 28 Demidenko ZN, Zubova SG, Bukreeva EI, Pospelov VA, Pospelova TV, Blagosklonny MV. Rapamycin decelerates cellular senescence. Cell Cycle. 2009 Jun;8(12):1888-95. https://doi.org/10.4161/cc.812.8606
  • 29 Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci USA. 2010 May;107(21):9660-4. https://doi.org/10.1073/pnas.1002298107
  • 30 Ali IK, McKendrick L, Morley SJ, Jackson RJ. Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation. EMBO J. 2001 Aug;20(15):4233-42. https://doi.org/10.1093/emboj/20.15.4233
  • 31 Saez I, Vilchez D. The mechanistic links between proteasome activity, aging and age-related diseases. Curr Genomics. 2014 Feb;15(1):38-51. https://doi.org/10.2174/138920291501140306113344
  • 32 Mazzotti DR, Guindalini C, Moraes WA, Andersen ML, Cendoroglo MS, Ramos LR et al. Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile. Front Aging Neurosci. 2014 Jun;6:134. https://doi.org/10.3389/fnagi.2014.00134
  • 33 Wang F, Nguyen M, Qin FX, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007 Aug;6(4):505-14. https://doi.org/10.1111/j.1474-9726.2007.00304.x
  • 34 Tucci P. Caloric restriction: is mammalian life extension linked to p53? Aging (Albany NY). 2012 Aug;4(8):525-34. https://doi.org/10.18632/aging.100481
  • 35 Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 2003 Mar;11(3):577-90. https://doi.org/10.1016/S1097-2765(03)00050-9
  • 36 Deng X, Gao F, Flagg T, Anderson J, May WS. Bcl2's flexible loop domain regulates p53 binding and survival. Mol Cell Biol. 2006 Jun;26(12):4421-34. https://doi.org/10.1128/MCB.01647-05
  • 37 Tomita Y, Marchenko N, Erster S, Nemajerova A, Dehner A, Klein C et al. WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization. J Biol Chem. 2006 Mar;281(13):8600-6. https://doi.org/10.1074/jbc.M507611200
  • 38 Alberts B, J.A., Lewis J, Raff M, Roberts K, Walter P, Biologia molecular da célula. 5a ed. Porto Alegre: Artmed; 2010.
  • 39 Hong SE, Heo HS, Kim DH, Kim MS, Kim CH, Lee J et al. Revealing system-level correlations between aging and calorie restriction using a mouse transcriptome. Age (Dordr). 2010 Mar;32(1): 15-30. https://doi.org/10.1007/s11357-009-9106-3
  • 40 Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R et al. Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet. 2006 Jul;2(7):e115. https://doi.org/10.1371/journal.pgen.0020115
  • 41 McCarroll SA, Murphy CT, Zou S, Pletcher SD, Chin CS, Jan YN et al. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. Nat Genet. 2004 Feb;36(2):197-204. https://doi.org/10.1038/ng1291