Envolvimento da via autofágica no envelhecimento bem-sucedido
Data
2015-09-30
Autores
Chaves, Carolina Fioroto 
Orientadores
D'Almeida, Vania
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O envelhecimento é um fenômeno no qual há o declínio dos processos essenciais para a sobrevivência celular. As principais vias que mantem a limpeza e a homeostase celular são a autofagia e o proteassomo. Investigamos estas vias em três diferentes grupos de indivíduos: Jovens (20-30 anos), Idosos (60-70 anos) e Longevos (80-105 anos) por meio da quantificação do proteassomo no plasma e da expressão de genes relacionados à maquinaria autofágica em sangue periférico. Nos níveis do proteassomo quantificados no plasma, não foram encontradas diferenças significativas entre os três grupos estudados, assim como não foram encontradas correlações entre os níveis de proteassomo e as idades dentro de cada grupo. Com relação à via autofágica, foi medida a expressão de 84 genes, sendo que destes, apenas 5 foram diferencialmente expressos: ATG4C (codifica proteína com atividade de protease, envolvido na formação do vacúolo autofágico; responsável pelo transporte de proteínas e; responsável pelas proteínas alvo da membrana/vacúolo) BCL2L1 (co-regulador da autofagia e apoptose), TP53 (co-regulador da autofagia e do ciclo celular; co-regulador da autofagia e apoptose), EIF2AK3 (co-regulador da autofagia e apoptose e indutor da autofagia por patógenos intracelulares) e EIF4G1 (regulador da autofagia em resposta a outros sinais intracelulares). Foi feita também análise de rede e de enriquecimento para observar as interações entre os genes diferencialmente expressos e os processos nos quais eles estão envolvidos. Observamos uma interação entre quatro dos cinco genes diferencialmente expressos, e a participação destes genes, seja direta ou indiretamente, no processo transcricional, sugerindo que a transcrição possa estar afetada pelo processo de envelhecimento. Foi verificado que os Longevos apresentaram tanto uma manutenção da expressão dos genes ligados à maquinaria autofágica, quanto uma manutenção dos níveis de proteassomo, em relação ao grupo Idoso, fatores estes que podem ser importantes para um envelhecimento bem-sucedido.
Aging is a phenomenon in which there is the decline of essential processes for cell survival. The main routes that maintain the cleaning and cellular homeostasis are autophagy and proteasome. These pathways were investigated in three different groups of subjects: young adults (20-30 years), older adults (60-70 years) and oldest old (80-105 years) by quantifying the proteasome in plasma and expression of genes related to the autophagic machinery in peripheral blood. In proteasome levels there were no significant differences among the groups, and there were no correlations between proteasome levels and ages within each group. Regarding the autophagic pathway, it was measured the expression of 84 genes, and of them only 5 were differentially expressed: ATG4C (encodes protein with protease activity, involved in the formation of autophagic vacuoles, responsible for transporting proteins, responsible for target proteins the membrane/vacuole) BCL2L1 (co-regulator of autophagy and apoptosis), TP53 (co-regulator of autophagy and cell cycle; coregulator of autophagy and apoptosis), EIF2AK3 (co-regulator of autophagy and apoptosis and autophagy inducer by intracellular pathogens) and EIF4G1 (regulator of autophagy in response to other intracellular signals). We also conducted network and enrichment analyses to observe the interactions between differentially expressed genes and processes in which they are involved. We observed an interaction between four out of the five differentially expressed genes, and these genes participate, directly or indirectly, in the transcription process, showing that this process might be affected by aging. We found that the oldest old subjects had both a maintenance of the expression of genes linked to the autophagic machinery and, the maintenance of the proteasome levels, compared to the elderly group, factors that may be important for successful aging.
Aging is a phenomenon in which there is the decline of essential processes for cell survival. The main routes that maintain the cleaning and cellular homeostasis are autophagy and proteasome. These pathways were investigated in three different groups of subjects: young adults (20-30 years), older adults (60-70 years) and oldest old (80-105 years) by quantifying the proteasome in plasma and expression of genes related to the autophagic machinery in peripheral blood. In proteasome levels there were no significant differences among the groups, and there were no correlations between proteasome levels and ages within each group. Regarding the autophagic pathway, it was measured the expression of 84 genes, and of them only 5 were differentially expressed: ATG4C (encodes protein with protease activity, involved in the formation of autophagic vacuoles, responsible for transporting proteins, responsible for target proteins the membrane/vacuole) BCL2L1 (co-regulator of autophagy and apoptosis), TP53 (co-regulator of autophagy and cell cycle; coregulator of autophagy and apoptosis), EIF2AK3 (co-regulator of autophagy and apoptosis and autophagy inducer by intracellular pathogens) and EIF4G1 (regulator of autophagy in response to other intracellular signals). We also conducted network and enrichment analyses to observe the interactions between differentially expressed genes and processes in which they are involved. We observed an interaction between four out of the five differentially expressed genes, and these genes participate, directly or indirectly, in the transcription process, showing that this process might be affected by aging. We found that the oldest old subjects had both a maintenance of the expression of genes linked to the autophagic machinery and, the maintenance of the proteasome levels, compared to the elderly group, factors that may be important for successful aging.
Descrição
Citação
CHAVES, Carolina Fioroto. Envolvimento da via autofágica no envelhecimento bem-sucedido. 2015. 108 f. Dissertação (Mestrado em Psucobiologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.