Submitted by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-04-18T12:45:57Z No. of bitstreams: 1 SimoneCruzLongattiDissertacao2015.pdf: 1831650 bytes, checksum: 1d47e365955c37dbb497ed07d699c22d (MD5) / Approved for entry into archive by Sara Ribeiro (sara.ribeiro@ucb.br) on 2017-04-18T12:46:06Z (GMT) No. of bitstreams: 1 SimoneCruzLongattiDissertacao2015.pdf: 1831650 bytes, checksum: 1d47e365955c37dbb497ed07d699c22d (MD5) / Made available in DSpace on 2017-04-18T12:46:06Z (GMT). No. of bitstreams: 1 SimoneCruzLongattiDissertacao2015.pdf: 1831650 bytes, checksum: 1d47e365955c37dbb497ed07d699c22d (MD5) Previous issue date: 2015-12-09 / Aging is a complex and multifaceted process that includes physiological, molecular and genetic changes that lead to functional decline of tissues and organs, leading to increased susceptibility to disease and consequent increase of mortality rates. In this context, chronic non-communicable diseases (NCDs) are often found in the elderly, especially the onco-hematologic diseases, including chronic lymphocytic leukemia (CLL). Considered as essentially a disease of the elderly, CLL is a disease of clonal lymphoid infiltration of B cells found in the bone marrow (BM), peripheral blood and lymph nodes, and characterized as the most common type of leukemia in Western countries. LLC expresses high levels of anti-apoptotic proteins, and decreased levels of proapoptotic proteins, which explains the exaggerated increase of mature B lymphocytes. In addition to changes protein levels, deregulation of microRNAs (miRNAs) have been associated with the LLC. Numerous miRNAs are associated with susceptibility to cancer, suggesting an important role in carcinogenesis. In addition, several miRNAs are also involved in the regulation pathways related to cell senescence and have effects on cell cycle progression, suggesting that miRNAs can be considered good biomarkers in the senescence process. The aim of the study was to evaluate the expression of miRNAs miR- 1248, miR-181a and miR-151a-3p by qPCR in patients with LLC and compare with the elderly group without the disease. The expression of miR-181a was significantly reduced in patients with CLL compared to individuals in the group without LLC. However, the study showed no difference in the expression of miRNAs in the groups with respect to age and sex. It is possible to suggest that these miRNAs can act as regulators likely in aging, however, future studies will determine the mechanism of expression of the same, and to discuss how best to use them as diagnostic and therapeutic tools for aging and age-related diseases such as CLL. / O envelhecimento ?? um processo complexo e multifatorial que inclui altera????es fisiol??gicas, moleculares e gen??ticas que levam ao decl??nio funcional de tecidos e ??rg??os, provocando o aumento da suscetibilidade ??s doen??as e consequente eleva????o das taxas de mortalidade. Nesse contexto, as doen??as cr??nicas n??o transmiss??veis (DCNT) s??o frequentemente encontradas em idosos, principalmente as doen??as onco-hematol??gicas, dentre elas a leucemia linfoc??tica cr??nica (LLC). Considerada essencialmente como uma doen??a de idosos, a LLC ?? uma patologia linf??ide de infiltra????o clonal de c??lulas B encontradas na medula ??ssea (MO), no sangue perif??rico e nos linfonodos, sendo caracterizada como o tipo mais comum de leucemia em pa??ses ocidentais. A LLC expressa n??veis elevados de prote??nas anti-apopt??ticas e n??veis diminu??dos de prote??nas pr??-apopt??ticas, o que explica o aumento exacerbado de linf??citos B maduros. Al??m das altera????es dos n??veis de prote??nas, a desregula????o de microRNAs (miRNAs) tem sido associada ?? LLC. In??meros miRNAs est??o associados ?? suscetibilidade ao c??ncer, sugerindo um importante papel na carcinog??nese. Al??m disso, v??rios miRNAs tamb??m est??o envolvidos na regula????o de vias relacionadas a senesc??ncia celular e t??m efeitos sobre a progress??o do ciclo celular, sugerindo que os miRNAs podem ser considerados bons biomarcadores no processo de senesc??ncia. O objetivo do estudo foi avaliar a express??o dos miRNAs miR-1248, miR-181a e miR- 151a-3p por meio da qPCR em portadores de LLC e comparar com o grupo de idosos sem a doen??a. A express??o do miR-181a foi significativamente reduzida nos pacientes com LLC quando comparada aos indiv??duos do grupo sem LLC. No entanto, o estudo demonstrou que n??o houve diferen??a na express??o dos miRNAs nos grupos em rela????o ?? idade e ao sexo. ?? poss??vel sugerir que esses miRNAs possam atuar como prov??veis reguladores no envelhecimento, por??m, estudos futuros poder??o determinar o mecanismo da express??o dos mesmos, bem como discutir a melhor forma de utiliz??-los como ferramentas diagn??sticas e terap??uticas para o envelhecimento e doen??as relacionadas ?? idade, como por exemplo a LLC.