Biomarcadores da longevidade humana e bioatividade do exopolissacarídeo botriosferana no envelhecimento

• Autor(a) principal: Sena, Geralda Gillian Silva
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7132
• topic: Human longevity; Botryosphaeran; Cytogenotoxicity; Glucolipidemic effect; Longevidade humana; Gene FOXO3; Botriosferana; Citogenotoxicidade; Efeito glicolipidêmico; Biotecnologia; 61

In the last decades it has been observed a world grow in elderly population associated with the increase of longevity. Multiple factors, among them, environmental, behavioral and genetic can influence human longevity. There is a great interest in improvement of natural products with functional and/or health proprieties. Fungal exopolysaccharides (EPS) as (1→3;1→6)-βD-glucan botryosphaeran, secreted by Botryosphaeria rhodina MAMB-05, are promising candidates for being considered modifiers of biological response. The present study aimed: a) to investigate in human possible longevity biomarkers through the frequency of polymorphisms at the genes FOXO3 (rs2802292), SOD2 (rs4880), APOE (rs429358 and rs7412) and SIRT1 (rs2273773) in a sample of elders of Grande Vitória, ES, as well as its state of oxidative stress and DNA integrity level; b) asses antimutagenic, mutagenic and cytotoxic of botryosphaeran in young and aged Swiss mice, from both gender, as well as its hypolipidemic, hypoglycemic and antiatherogenic potential in older male LDL receptor knockout (LDLr-/-) animals and its background (C57BL/6). To achieve the objectives: a) in elderly sample, it was characterized demographic, socioeconomic, anthropometrics, biochemical, clinics and life style data. Genetic polymorphisms were analyzed through real time polymerase chain reaction; the malondialdehyde, by high performance liquid chromatography and genomic damage, by alkaline comet assay in groups of long-lived individuals and controls (≥ 85 years and 70-75 years); b) with animals - botryosphaeran, was administrated, by gavage (doses of 7.5, 15 and 30 mg/kg b.w. per day) in a 30-day pretreatment in 30-day protocol (young mice) and 15-day protocol (older mice) to investigate its mutagenic and anticytogenotoxic potential against damages induced by cyclophosphamide. The micronucleus assay was carried through erythrocytes of peripheral blood and bone marrow from mice. Glucolipidemic and atheroprotective effects of EPS (30 mg/kg b.w. per day, by gavage) among LDLr-/- animals, that received atherogenic diet, were verified by plasmatic glucose measure and lipidic profile after 15 days of treatment, with commercial colorimetric kits. The atherosclerotic lesion was quantified by aortic lipidic deposition analysis (en face), with Oil-Red-O. The statistical analysis was performed by χ² test, Fisher exact test, Tukey test, t Student, Mann-Whitney and Hardy-Weinberg Equilibrium (H-WE) (p<0.05). Among oldest-old individuals and controls, the plasmatic levels of malondialdehyde and DNA damage had similar values. It was observed a positive association between rs2802292 FOXO3 and longevity. Biochemical and anthropometric characteristics, related to successful aging, showed significant results. In in vivo assay, botryosphaeran, in the 3 doses, 14 it was not mutagenic and still reduced the percentage of damage between young and older animals (Swiss, C57BL/6 e LDLr-/-). There was reduction in glucose plasmatic levels (36%), improved in lipidic profile (reductions of 53.8-84.3%) and decreased of aortic lipidic deposition (32.8%) in the LDLr-/- atherosclerotic mice treated with EPS. Our results provide new insights of human longevity, in Brazilian population, and contribute to a promising future of genomic geriatric and personalized medicine. Moreover, it does indicate that botryosphaeran has relevant biologic effect, making it a promising candidate for new therapeutic products development.