From Bioenergetics to Cardiac Function and Thymocyte differentiation in the Aging Population. Dr. Daniel J. Guerra 02 December 2020.

In today's lecture, Dr Guerra explains how subclinical hypothyroidism obtains increased serum thyrotropin (thyroid stimulating hormone, TSH) with flat levels of of free thyroxin (T4) and biologically active free triiodothyronine (T3) in the elderly;β1 adrenergic receptors, sodium/potassium ATPase, voltage-gated potassium channels, malic enzyme and atrial and brain natriuretic factor all respond favourably to thyroxin and hese proteins form the primary architecture of the cardiomyocyte and determine contractile strength. ATP drives muscle contraction/relaxation thus active  mitochondrial nadh  oxidation is essential for healthy aging. Ketone and free fatty acid oxidation decreases with aging while glucose oxidation reciprocally increases while thyroid hormone levels decline with aging, suggesting that myocardial metabolic pathology is linked phenomenologically to subclinical hypothyroidism.

Indeed,thyroid hormone deficiency found in aging populations inhibits fatty acid oxidation through transcriptionally mediated downregulation of PPARα where this transcription factor normally suppresses PDK4, which allows increased PDH. This suggests that aging correlates with decreasing  fatty acid oxidation which is associated with reduced cardiac function.  The aged heart relies on lactate, glucose and pyruvate in place of  fatty acids and the PDH complex plays a central role in the modulation from fatty acid oxidation to glucose oxidation in the mitochondria to finally anaerobic glycolysis in the aging heart.

T lymphocyte maturation and expansion also follows a switch in carbon energy utilization so the two systems function in contrarion regulation, leading to decreased cardiac output with a declining naive T cell population thus losing the regulated induction of inflammation from diverging metabolic sequalae in the aging human.

PLoS One. 2013; 8(6): e65532.

Int J Mol Sci. 2020 Nov; 21(21): 7972

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