Poster Topical Area: Aging and Chronic Disease
Poster Board Number: 96
Contrary to their indispensability for the sustenance of life, diets low in Met and without Cys (SAAR) confer a spectrum of benefits including lifespan extension and changes in energy metabolism - SAAR phenotype. However, repletion of SAAR diet with Cys reverses some benefits. It is unclear whether this disparity is due to increased bioavailability of Cys per se, or of Met, which could occur due to the sparing effect of Cys on Met requirements. As both of them have distinct biological roles, we hypothesized that the SAAR phenotype is a combination of the discrete effects of low Met and low Cys.
a) To determine if Met and Cys exert discrete effects on biomarkers of SAAR phenotype.
b) To find minimal obligatory dose of Met (MoM), which recapitulates SAAR phenotype in the presence of Cys.
Two cohorts of male F344 rats, sequentially, were fed diets titrated with Met (Cohort 1) and Cys (Cohort 2) for 12-weeks. In Cohort 1, rats were fed control diet (CD), SAAR diet, and four different diets (MT1 to MT4) with decreasing levels of Met in the presence of excess Cys (Table 1). MoM was determined by comparing growth rate, fasting glucose, plasma protein, leptin, IGF1, FGF21, and adiponectin in SAAR group with those in MT1-MT4. In Cohort 2, rats were fed CD, SAAR, and five different diets containing MoM obtained from Cohort 1 and decreasing levels of Cys (CT1 to CT5, Table 1). Same biomarkers were measured in Cohort 2.
Compared to CD, SAAR in both cohorts had slower growth rates (58%), higher levels of FGF21 (179%) and adiponectin (329%), lower levels of IGF-1 (64%) and leptin (48%). All biomarkers exhibited dose response to dietary content of either Met or Cys. Within the doses tested, a direct dose response for growth rate, fasting glucose, plasma protein, IGF1, leptin and an inverse dose response for FGF21 was observed with Met content. Adiponectin exhibited a modest response for Met but a strong response for Cys content. A diet with 0.07% of Met (MoM) and 0.5% of Cys elicits similar changes in biomarkers investigated as observed in a typical SAAR.
Preliminary data indicates that SAAR phenotype is a combination of decreased bioavailability of both sulfur amino acids, which exert discrete effects on biomarkers. SAAR phenotype can be recapitulated even in the presence of Cys if Met is decreased to 0.07%.
Orentreich Foundation for the Advancement of Science
Cold Spring, New York