BACKGROUND: Subclinical hypothyroidism occurs during aging in humans and mice 
and may contribute to the development of heart failure. Aging also impairs 
myocardial fatty acid oxidation, causing increased reliance on flux through 
pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the 
metabolic changes in aged hearts make them less tolerant to acutely increased 
work and that thyroid hormone supplementation reverses these defects.
METHODS: Studies were performed on young (Young, 4-6 months) and aged (Old, 
22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). 
Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload 
only). Function was measured in isolated working hearts along with substrate 
fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate 
with (13)C labeled lactate, pyruvate, glucose and unlabeled palmitate and 
insulin.
RESULTS: Old mice maintained cardiac function under standard workload 
conditions, despite a marked decrease in unlabeled (presumably palmitate) Fc and 
relatively similar individual carbohydrate contributions. However, old mice 
exhibited reduced palmitate oxidation with diastolic dysfunction exemplified by 
lower -dP/dT. Thyroid hormone abrogated the functional and substrate flux 
abnormalities in aged mice.
CONCLUSION: The aged heart shows diminished ability to increase cardiac work due 
to substrate limitations, primarily impaired fatty acid oxidation. The heart 
accommodates slightly by increasing efficiency through oxidation of carbohydrate 
substrates. Thyroid hormone supplementation in aged mice significantly improves 
cardiac function potentially through restoration of fatty acid oxidation.