Aging-Related Correlation between Serum Sirtuin 1 Activities and Basal Metabolic Rate in Women, but not in Men

Abstract

Sirtuin (SIRT) is a well-known regulator of nutrients (glucose and lipid) metabolism and aging processes in nicotinamide adenine dinucleotide (NAD) +-dependent (as protein deacetylase and/or mono adenosine diphosphate [ADP] ribosyltransferase) and-independent ways [3,4]. Among 7 SIRTs, SIRT1 was extensively investigated, and its regulatory roles and working mechanisms were identified relating to the effect of caloric restriction on life span [5-7]. SIRT1 exerts its effects by activating downstream targets (e.g. forkhead box O1, peroxisome proliferator-activated receptor (PPAR) gamma, coactivator 1 alpha, and PPAR gamma), which differed by types of target tissues and stimulus [8-10]. Although the implication that SIRT1 can be a probable biomarker of aging is evident, little evidence was reported to support the hypothesis in human studies. Enormous efforts were invested to identify metabolic biomarkers of aging utilizing the up-to-date technologies. Several models for estimating biological age (e.g. vessel/vascular age and hormonal age) were already introduced and applied in clinical setting [11-15]. A recent remarkable work developed the metabolic age score, the way to measure biological age via metabonomics [16]. Considering the significance of SIRT in aging, research should focus to apply SIRT to reflect aging and its related physiological/pathophysiological processes. However, evidence has not yet reported to validate serum SIRT activity as a biomarker of aging. Therefore, we hypothesized that SIRT is a potential biomarker reflecting aging. To test this hypothesis, we identified the pattern of serum SIRT1 activity according to age and sex, and investigated how serum SIRT1 activity was correlated with other metabolic parameters in Korean adults. Because aging homeostasis is different from normal metabolic homeostasis, we need to identify the appropriate biomarkers for aging homeostasis, and try to provide evidence to address whether serum SIRT activity may be utilized as a biomarker of aging homeostasis. MATERIALS AND METHODS Study subjects Fasting serum samples and a subset of data from 250 healthy adults (122 men and 128 women) were provided by the Biobank of Jeju National University Hospital, a member of the Korea Biobank Network. Serum samples were collected from subjects who visited the healthcare center of Jeju National University Hospital from 2009 to 2015. Fifty subjects for each age group (20's, 30's, 40's, 50's, and over 60's) were randomly selected and provided for analysis. The current research involving human participants has been reviewed by the Institutional Review Board (IRB) of Seoul Women's University (IRB-2015A-10). Measurements A subset of routine laboratory data was provided by the Biobank of Jeju National University Hospital. The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), atherogenic index (AI), and low-density lipoprotein-cholesterol (LDL-C) were calculated by the following equations [17]: AAR = AST (IU/L)/ALT (IU/L) AI = (Total cholesterol [TC; mmol/L] − high-density lipoprotein-cholesterol [HDL-C; mmol/L])/HDL-C (mmol/L) LDL-C (mg/dL) = TC − HDL-C (mg/dL) − triglyceride (TG; mg/dL)/5.0