Mitochondrial Metabolism in Aging Heart

Abstract

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction.

The role of mitochondria in cardiac development and protection

“…Both age-related decline in cardiac contractility as well as developing cardiomyopathy result in specific loss of IFM function [71,138], which might be possible to counteract by promoting mitochondrial biogenesis, resulting not only in increased OXPHOS but also activating mitochondrial fission [4,62]. Interestingly, in mitochondrial fusion-deficient mice already a change to high-fat diet was enough to alter cardiac metabolism and prevent the development of cardiomyopathy [75].…”

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

“…We next sought to observe cytochrome C oxidase activity, which is associated with oxygen consumption and the aging process. [23][24][25] COX staining was performed as described previously. The number of COX-positive cells was counted and normalized to total cell numbers.…”

A new strategy to decrease cardiac injury in aged heart following ischaemia-reperfusion: enhancement of the interaction between AMPK and SIRT1

“…1 Although many therapeutic interventions can effectively decrease cardiac injury in younger adult hearts, strategies to decrease cardiac injury in aged hearts are still limited. 1 Therefore, understanding the mechanisms of injury in the aged heart during IR is critical to develop potential strategies to protect the high-risk aged heart.…”

“…1 Although many therapeutic interventions can effectively decrease cardiac injury in younger adult hearts, strategies to decrease cardiac injury in aged hearts are still limited. 1 Therefore, understanding the mechanisms of injury in the aged heart during IR is critical to develop potential strategies to protect the high-risk aged heart. 2 The impairment of substrate flexibility (balance between glucose usage and fatty acid oxidation) contributes to cardiac injury during IR as well as heart failure development.…”

“…Mitochondrial dysfunction contributes to increased cardiac injury in aged hearts. 1 Aging impairs electron transport chain (ETC) activity in the interfibrillar population of mitochondria located between the fibrils (IFM). The Complex III activity is decreased in IFM isolated from the aged hearts.…”