Aging Increases Susceptibility to Develop Cardiac Hypertrophy following High Sugar Consumption

Figures

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  Figure 1. Changes in body weight (A) and maximal isometric torque of plantarflexors (B) in 24-month-old CB6F1 mice consuming either standard chow or high sucrose (HS) diet for 1 or 4 weeks. Differences in heart (C) and liver (D) mass between groups. Data expressed as mean ± SD. Significant differences to age-matched chow are indicated by * p < 0.05, ** p < 0.01, non–significant effects by "ns".

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  Figure 2. Differences in food intake (A), changes in body weight (B), and non-fasted serum glucose, insulin, and serum amyloid A (SAA) (C–E) between young adult and old adult male CB6F1 mice consuming regular chow or HS diet, treated with or without elamipretide (ELAM). Food intake was recorded per cage housing both saline and ELAM–treated groups. Two-way ANOVA was used to detect differences between age and treatment (Tx) groups. Significant effects are denoted by p–value and non–significant effects by “NS”. Data expressed as mean ± SD.

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  Figure 3. Representative images of dissected hearts from each group on the same scale (A). Heart mass normalized to tibial length (B). Gene expression of hypertrophy marker myosin heavy chain 7 (Myh7) is expressed relative to young–chow (C). In vivo measures of cardiac parameters by echocardiography include left ventricular posterior wall dimension (D). Ea/Aa ratio as indicator of diastolic function (E), and ejection fraction and fractional shortening as indicators of systolic function (F,G). Significant differences between old and young are indicated by age effect; differences between old–chow and old–HS are indicated with smaller brackets containing p–values if slightly above p > 0.05 or asterisks if significant, p < 0.05. Data expressed as mean ± SD.

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  Figure 4. Mitochondrial respiration and hydrogen peroxide production. Mitochondrial respiration using Oroboros O2K (A,C) and protein content of electron transport chain complexes assessed by immuno blot (B) were measured in isolated mitochondria from freshly isolated hearts. The rise in respiration with the addition of fatty acid (FA) octanoylcarnitine in the presence of complex I substrates and ADP was quantified for each age and treatment group (C). The ratio of reactive oxygen species (ROS) to oxygen being consumed by isolated mitochondria (D). Significant differences between old and young are indicated by age effect; differences between old-chow and old-HS are indicated with smaller brackets containing p–values between 0.05–0.1 or asterisks if significant, p < 0.05, or NS if p–value is above 0.1. Data expressed as mean ± SD.

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  Figure 5. Gene expression and histology of heart tissue. (A) Differences in metabolic and (B) inflammatory genes between diet and age groups; (B). Age and diet effects are indicated with “ns” if above 0.1, with p-value if between 0.05–0.1, and significant if below 0.05. Data expressed as mean ± SD.

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  Figure 6. Histological analysis of heart tissue. Sections of heart apex stained with H&E (A) and Picrosirius Red (C) to measure cardiomyocyte size (B) and collagen content (D). Significant differences between old and young are indicated by age effect p < 0.05. Differenced between old–chow and old–HS are indicated with a smaller bracket containing the p–value or asterisk if <0.05. Data expressed as mean ± SD.