Functional investigation of the effect of aging on the rhythmicity of in vitro SIRT2 and miR-1275 expression

• Grant number: 14/25630-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2015
• End date: December 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sergio Tufik
• Grantee: Juliana Ramirez Arruda
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The increase in life expectancy in the last decades has resulted in a scenario in which the elderly constitutes a growing proportion of the population. Several studies have targeted the population aging, and those which aims at the identification of molecular mechanisms and behaviors associated with successful aging are more and more evident. Some physiological patterns and lifestyle habits have been linked to human longevity, such as the regularity of circadian rhythm and sleep patterns, besides the low calorie intake (caloric restriction). Many molecules have been identified as regulators of aging and life expectancy, being sirtuins the most studied ones. The gene expression of SIRT2, a histone deacetylase, was found to be increased in oldest old individuals (over 85 years) compared to young and older adults, and the expression of miRNA-1275, a potential epigenetic regulator of that gene, is reduced in these individuals. Therefore, the present study aims to investigate the regulation of SIRT2 expression by miRNA-1275 and its relationship to the increased life expectancy, as well as to investigate the effect of age on the circadian expression of these molecules in culture derived leukocytes from young adults, older adults and oldest old individuals submitted to a shock with fetal bovine serum. Given the recent evidence about the importance of proper maintenance of the circadian system for longevity, we expect that the oldest old will have greater robustness of the molecular circadian rhythm compared to the older adults.