Metabolic Shifts during Aging and Pathology

Abstract

The heart is a very special organ in the body and has a high requirement for metabolism due to its constant workload. As a consequence, to provide a consistent and sufficient energy a high steady-state demand of metabolism is required by the heart. When delicately balanced mechanisms are changed by physiological or pathophysiological conditions, the whole system’s homeostasis will be altered to a new balance, which contributes to the pathologic process. So it is no wonder that almost every heart disease is related to metabolic shift. Furthermore, aging is also found to be related to the reduction in mitochondrial function, insulin resistance, and dysregulated intracellular lipid metabolism. Adenosine monophosphate-activated protein kinase (AMPK) functions as an energy sensor to detect intracellular ATP/AMP ratio and plays a pivotal role in intracellular adaptation to energy stress. During different pathology (like myocardial ischemia and hypertension), the activation of cardiac AMPK appears to be essential for repairing cardiomyocyte’s function by accelerating ATP generation, attenuating ATP depletion, and protecting the myocardium against cardiac dysfunction and apoptosis. In this overview, we will talk about the normal heart’s metabolism, how metabolic shifts during aging and different pathologies, and how AMPK regulates metabolic changes during these conditions.

Sestrin2 prevents age-related intolerance to post myocardial infarction via AMPK/PGC-1α pathway

“…The beneficial effects of Sestrin2 against ischemic injury by post-MI are mediated through AMPK regulating PGC-1α [13,31]. The impaired ischemic AMPK activation observed in aged and Sesn2 KO hearts facilitated down-regulation of PGC-1α during post myocardial infarction (post-MI) that could potentially augment generation of more reactive oxygen species (ROS) in the mitochondria to damage cardiomyocytes [11]. The impaired mitochondrial related proteins such as TFAM and UCP2 in aged WT and Sestrin2 KO hearts as compared to young hearts implicates that more mitochondria dysfunction/damage may occur in aged WT and Sestrin2 hearts versus young WT hearts.…”

“…The mitochondria are the major organelles that produce reactive oxygen species (ROS) [11]. The ROS-detoxifying system and mitochondrial biogenesis may play vital roles as endogenous protective mechanisms during myocardial ischemia [11].…”

“…The ROS-detoxifying system and mitochondrial biogenesis may play vital roles as endogenous protective mechanisms during myocardial ischemia [11]. There is evidence that the peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a powerful stimulator of mitochondrial biogenesis and gene transcription in the liver, heart, and skeletal muscle [12].…”

Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation

“…66 Stress-related metabolic changes and altered activity of AMP-activated protein kinase (AMPK) are proposed to play an important role in the pathogenesis of AF 67 because AF is characterized by irregular contractions of atrial cardiomyocytes and increased energy demands. Currently, laboratory evidence suggests a potential role of AMPK in the pathophysiology of AF.…”

The structure-activity relationship of ginsenosides on hypoxia-reoxygenation induced apoptosis of cardiomyocytes

“…Prolonged ischemia causes a drop in ATP levels and an increase in anaerobic metabolism, which results in tissue damage/death [21,22]. Reperfusion of acute or chronic ischemic myocardium is necessary for restoring the flow of blood in order to salvage the myocardium.…”