Exercise, Nrf2 and Antioxidant Signaling in Cardiac Aging.

Madhusudhanan Narasimhan,Namakkal S. Rajasekaran

doi:10.3389/fphys.2016.00241

Abstract

Aging is represented by a progressive decline in cellular functions. The age-related deformities in cardiac behaviors are the loss of cardiac myocytes through apoptosis or programmed cell death. Oxidative stress (OS) and its deleterious consequence contribute to age-related mechanical remodeling, reduced regenerative capacity, and apoptosis in cardiac tissue. The pathogenesis of OS in the elderly can predispose the heart to other cardiac complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and so on. At the molecular level, oxidant-induced activation of Nrf2 (Nuclear erythroid-2-p45-related factor-2), a transcription factor, regulates several genes containing AREs (Antioxidant Response Element) and bring the respective translates to counteract the reactive radicals and establish homeostasis. Myriad of Nrf2 gene knockout studies in various organs such as lung, liver, kidney, brain, etc. have shown that dysregulation of Nrf2 severely affects the oxidant/ROS sensitivity and predispose the system to several pathological changes with aberrant cellular lesions. On the other hand, its gain of function chemical interventions exhibited oxidant stress resistance and cytoprotection. However, thus far, only a few investigations have shown the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. Therefore, here we review the involvement of Nrf2 signaling along with its responses and ramifications on the cascade of OS under acute exercise stress (AES), moderate exercise training (MET), and endurance exercise stress (EES) conditions in the aging heart.

Highlights

Redox homeostasis is a delicate steadiness between oxidants and antioxidants in a setting of intracellular milieu
Given that in the physically fit who undergoes progressive training, there is a decreased incidence of oxidative stress (OS) based pathologies due to establishment of adaptive resistance to OS along with induction of trophic factors and oxidative-damage repairing systems (Radak et al, 2001, 2009; Katzmarzyk and Janssen, 2004; Halestrap et al, 2007; Tremblay et al, 2007; van Praag, 2008), this review aims to focus on the systematic functions of nuclear factor erythroid-2-p45-related factor-2 (Nrf2) with respect to different mode of exercises such as acute exercise stress (AES), endurance exercise stress (EES) and moderate exercise training (MET), and sketch the importance of maintaining “OPTIMAL” Nrf2 expression for the healthy regulation of redox homeostasis under disparate provocations in the cardiac system (Figure 2)
Abnormal levels of ROS are harmful and induce pathological cellular signaling, mild to modest concentrations that are comparable to the levels generated during acute to MET are likely to prime the transactivation of functional antioxidant adaptation

Summary

Introduction

Redox homeostasis is a delicate steadiness between oxidants and antioxidants in a setting of intracellular milieu. Human cells constantly undergo numerous chemical reactions and modifications every second requiring the constant need for oxygen and other compounds for a plethora of processes These obligatory processes involving oxygen could produce highly reactive oxygen species within the cell which when uncontrolled leads to oxidative stress (OS) (Uttara et al, 2009). The role of oxygen and oxygen-related processes are major determinants of its vitality wherein, a moderate tilt in the redox state of the cell may tip toward the increased production of oxidants causing oxidative damage leading to cardiac dysfunction and heart failure (Capell et al, 2007; Zhou et al, 2014)

Objectives

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Conclusion