O avanço da idade induz alterações na organização da cromatina e na ploidia de neurônios corticais de camundongos

• Autor(a) principal: Rodrigues, Henrique Ferreira
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFU
• Texto Completo: https://repositorio.ufu.br/handle/123456789/12384; https://doi.org/10.14393/ufu.di.2013.106
• topic: Cromatina; Envelhecimento; Epigenética; Neurônios; Poliploidia; Aging; Chromatin; Epigenetics; Neurons; Polyploidy; CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR

Aging is a process inherent to all living beings and constitutes a major risk factor for several degenerative and chronic diseases. It is characterized by a series of cellular alterations which lead to impaired normal tissue function with loss of its regenerative capacity. In this context, chromatin organization plays a major role in the mechanisms of aging, because it regulates gene expression, repair of macromolecules, and accessibility of genotoxic agents to DNA. Epigenetic mechanisms, such as DNA methylation and histone post-translational modifications (PTMs) are the main regulators of chromatin structure. Previous studies have described alterations on chromatin organization and epigenetic marks along aging. Thus, the knowledgement of the association between chromatin structure and aging is fundamental for the development of treatments that would increase life quality on the elderly population and delay or prevent the onset of several age-associated disorders, such as cancer, Alzheimer s disease and others. In this context, the objective of this work was to evaluate the structural and epigenetic alterations of nuclei of cortical neurons from mice with the advancing of age. To this end, isolated neuronal nuclei were Feulgen-stained, followed by image analysis to evaluate chromatin organization (analyzed also by enzymatic digestion kinetics with nuclease) and DNA content (analyzed also by flow cytometry), in addition to biochemical assays (SDS-PAGE and westernblotting) to quantify epigenetic marks. Results indicate significant alterations on chromatin organization of cortical neurons from mice with advancing age, whose fibers seem to undergo unpackaging, as well as increased levels of the epigenetic mark H3K9Ac, which is associated with unpackaged chromatin. Additionally, there is evidence that neurons undergo polyploidy, according to previous data on hepatocytes, being this polyploidy increased with increasing age. Since increased transcriptional activity is not characteristic of aged cells, the decreased chromatin packaging state may be correlated with impaired genome stability, along with activation of repair mechanisms triggered by the accumulation of DNA damage during life span, which is characteristic of aged cells.