Obesity Paradox in Caucasian Seniors: Results of the PolSenior Study.

OBJECTIVES: To investigate the influence of overweight and obesity on general performance and mortality in seniors. DESIGN: Cross-sectional multidisciplinary study on ageing of the Polish population. SETTING: Community-dwelling individuals aged 65 years or older, selected using three-stage stratified, proportional draw. PARTICIPANTS: 4944 Polish Caucasian seniors, aged 65 years or older recruited between October 2007 and October 2010. MEASUREMENTS: All study subjects underwent measurement of body mass index (BMI), waist circumference (WC), and arm circumference (AC). The physical and cognitive performance was evaluated using the Katz Activities of Daily Living (ADL) score and Mini-Mental State Examination (MMSE), respectively. Morbidity data were obtained from a medical questionnaire. Mortality data were obtained from the Population Register of Poland between October 2015 and October 2018. RESULTS: Increasing age was associated with a decreased prevalence of obesity (all p<0.001). Higher BMI, WC and AC values were associated with higher ADL and MMSE scores (all p<0.001). On multivariate analysis, all three body measurements in women remained independent predictors of the ADL score (BMI p=0.002, WC p=0.005, AC p<0.001) and MMSE score (p<0.001, p=0.003, p<0.001). In men, physical functioning was associated with AC (p=0.003), and cognitive status was associated with AC (p<0.001) and BMI (p=0.013). There was no association between general obesity, abdominal obesity, or AC with several aging-related adverse conditions. Kaplan-Meier survival curves showed that overweight and obesity were associated with the lowest mortality. On multivariate analysis, BMI and AC values remained independent predictors of mortality. In successfully aging individuals, neither BMI, WC, nor AC remained such predictors. CONCLUSIONS: Overweight and obesity in Caucasian seniors are not associated with deterioration of physical and cognitive function or with increased mortality.

SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status.

BACKGROUND/OBJECTIVE: Given their importance in the regulation of metabolism, sirtuins (SIRTs) constitute promising subjects of research on the pathogenesis of obesity and the metabolic syndrome. The aim of this study was to assess whether obesity in humans is associated with changes in the expression of SIRT genes in adipose tissue and whether epigenetic mechanisms, DNA methylation and microRNA (miRNA) interference, mediate in this phenomenon. SUBJECTS/METHODS: The expression of SIRTs and of SIRT1 and SIRT7 mRNA-interacting miRNAs was evaluated by real-time PCR in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 58 obese (body mass index (BMI) >40 kg m-2) and 31 normal-weight (BMI 20-24.9 kg m-2) individuals. The methylation status of SIRTs was studied by the methylation-sensitive digestion/real-time PCR method. RESULTS: SIRT1 mRNA levels were lower in adipose tissues of obese patients than of normal-weight controls (VAT: P=0.0002, SAT: P=0.008). In contrast, expression of SIRT7 was higher in adipose tissues of obese patients than in the control group (VAT: P=0.001, SAT: P=0.008). The mean methylation of the SIRT1 and SIRT7 CpG islands was similar in tissues with high and low expression of these genes, and there was no correlation between the level of expression and the level of methylation. On the other hand, expression of SIRT1 in VAT of obese subjects correlated negatively with the expression of miR-22-3p (P<0.0001, rs=-0.514), miR-34a-5p (P=0.01, rs=-0.326) and miR-181a-3p (P<0.0001, rs=-0.536). In turn, expression of SIRT7 in VAT of slim individuals correlated negatively with the expression of miR-125a-5p (P=0.003, rs=-0.562) and miR-125b-5p (P=0.018, rs=-0.460). CONCLUSIONS: We observed obesity-associated downregulation of SIRT1 and upregulation of SIRT7 mRNA levels that were not associated with the methylation status of their promoters. We found a negative correlation between mRNA levels of SIRT1 in VAT of obese individuals and SIRT7 in VAT of the normal-weight subjects and expression of the relevant miRNAs.