Perfil imunológico e composição da microbiota como biomarcadores do envelhecimento saudável.

• Ano de defesa: 2016
• Autor(a) principal: Gabriela da Silveira e Nunes
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Bioquímica e imunoligia; Microbiota; Biomarcadores; Citocinas; Bioquímica e imunologia; Envelhecimento saudável
• Link de acesso: http://hdl.handle.net/1843/BUOS-B27NPX

Aging is a complex phenomenon characterized by changes in the physiological systems of the body and it is associated with several alterations in the phenotype, repertoire and activation status of leukocytes as well as in the cytokine profile produced by these cells. The alteration of the cytokine network seems to be responsible for a chronic proinflammatory status, known as inflammaging. This chronic inflammation has been described as a combination of dysfunctional immunity associated with frailty and morbidity in the elderly. Several key mechanisms such as inflammation and altered microbiota composition are common during biologic aging and also in individuals with hypertension. The impact of age-related changes on cytokine global profiles of healthy Brazilian individuals at several age intervals (085 years) (population 1) were characterized using short-term cultures of whole blood cells samples and single-cell flow cytometry. In newborns and elderly the contribution of innate immune cells (neutrophils and NK cells) were prominent in the cytokine profile. Adult individuals presented a balanced profile with equal contribution of both compartments (innate and adaptive cells) and both categories of cytokines (inflammatory and regulatory). Considering the high prevalence of Hypertension in Brazilians adults, we characterize the cytokine profile and the composition of microbiota in Brazilian subjects categorized by presence of Arterial Hypertension. Samples were collected from 80 Brazilian subjects with age between 26 to 87 years (population 2). Production of IFN-, TNF, IL-17A, IL-6, IL-10, IL-4 and IL-2 in PBMC supernatant was measured using CBA and flow cytometry.Fecal microbiota composition was analyzed using high-throughput Illumina sequencing of 16S rRNA gene. Hypertension-bearing group was characterized by a reduction in microbiota diversity, with higher Firmicutes/Bacteroidetes (F/B) ratio, contraction of bacteroidetes population and of the well-known butyrate producers Lachnospiraceae family, Roseburia, Coprococcus. Moreover, the hypertension group showed a higher TNF/IFN ratio and a more inflamed profile compared to the control group. These variations were independent of age. Taken together, our results support the hypothesis that aging is not associated with a progressive decline in cytokine production by all leukocyte subsets but with distinct fluctuations of cytokines produced at various time points during life. Moreover, our findings showed that individuals classified as healthy although bearing sub-clinical hypertension presented inflammatory alterations and disbiosis, which points them as the borderline group between health and frailty during senescence