Poster Topical Area: Energy and Macronutrient Metabolism
Location: Hall D
Poster Board Number: 464
CR is the most potent, robust, and reproducible known means of extending longevity and decreasing morbidity in lab rodents. Despite 80+ years of research, the relevance of this observation for humans remains unknown, but it is supported by the established link between obesity and morbidity in humans.
The MEC-APS investigated metabolites associated with NAFLD – the most common cause of chronic liver disease worldwide – across five major U.S. racial/ethnic groups, which vary in NAFLD frequency by a 2.5 fold. Although NAFLD is obesity-associated, prediction of NAFLD by total adiposity, including proxies such as weight and BMI, is not strong and differs across race/ethnic groups<./p>
The MEC has followed 215,000 Hawaii and Los Angeles residents of African, Japanese, European, Latino, and Native Hawaiian ancestry since 1993-1996. In the MEC-APS, we measured liver fat using abdominal MRI and total body fatness by DXA in a cross-sectional subset of 1781 healthy women and men aged 60-77 years with BMIs of 17-46 kg/m2. Redox active plasma metabolites were assessed using HPLC separations with coulometric electrode array detection. Statistics: Mann-Whitney U, regression, AUROC.
Of 16 metabolites statistically associated with NAFLD, seven were previously linked to CR in studies of ad libitum fed and CR FBFN1 rats (males/females, different ages and extents and durations of CR). Strikingly, the strongest three NAFLD markers (p-7 in both sexes) were all previously CR-linked; all three are endogenous, very low concentration in plasma, structurally unidentified molecules that are followed using chromatographic and redox signatures. AUROCs for NAFLD (~0.75 in women/~0.85 in men) are comparable with the best available markers. AUROCs are essentially equal across liver fat cut-offs (4.0% to 6.5%) near the standard clinical threshold for NAFLD (>5.5%), suggesting robustness and the potential to recognize at-risk individuals. Limiting analysis to individuals who meet NAFLD alcohol consumption criteria strengthened the associations, suggesting that the markers capture the metabolic milieu specific to NAFLD, not overt fatty liver disease itself.
Biomarkers of CR in rats predict NAFLD men and women from five ethnic groups in the MEC-APS.
Harvard Medical School/Brigham and Women's Hospital