Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging.

Yue Quan,Junteng Zhou,Yanguo Xin,Xiaojing Liu,Geer Tian

doi:10.1155/2020/9423593

Yue Quan, Junteng Zhou + Show 3 more

Open Access

https://doi.org/10.1155/2020/9423593

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Abstract

Mitochondrial DNA (mtDNA) damage is associated with the development of cardiovascular diseases. Cardiac aging plays a central role in cardiovascular diseases. There is accumulating evidence linking cardiac aging to mtDNA damage, including mtDNA mutation and decreased mtDNA copy number. Current wisdom indicates that mtDNA is susceptible to damage by mitochondrial reactive oxygen species (mtROS). This review presents the cellular and molecular mechanisms of cardiac aging, including autophagy, chronic inflammation, mtROS, and mtDNA damage, and the effects of mitochondrial biogenesis and oxidative stress on mtDNA. The importance of nucleoid-associated proteins (Pol γ), nuclear respiratory factors (NRF1 and NRF2), the cGAS-STING pathway, and the mitochondrial biogenesis pathway concerning the development of mtDNA damage during cardiac aging is discussed. Thus, the repair of damaged mtDNA provides a potential clinical target for preventing cardiac aging.

Highlights

Cardiovascular diseases (CVDs) account for 31% of all deaths worldwide [1]
The proliferator-activated receptor gamma coactivator-1α (PGC-1α) activity is regulated via phosphorylation by some signaling pathways, including Akt, AMPK, deacetylation of Sirtuin (SIRT1/3) [95], and mitogen-activated protein kinase (MAPK) p38 (Figure 3)
Cardiac aging resulting in defects in cardiac mitochondrial function centers on the Mitochondrial DNA (mtDNA) damage

Summary

Introduction

Cardiovascular diseases (CVDs) account for 31% of all deaths worldwide [1]. Age is widely recognized as the leading risk factor for CVDs. The ventricular and valvular changes above make the aged heart more vulnerable to stress and contribute to the increased mortality and morbidity of CVDs in the elderly [3, 4]. The Drosophila melanogaster heart has a similar molecular structure and basic physiology as the human heart Both fly and human hearts experience age-related morphological and functional decline. Aged rat hearts demonstrate cardiomyocyte hypertrophy, increased LV fibrosis, and impairment of systolic and diastolic function [4]. Mitochondrial-derived oxidative stress plays a vital role in cardiac aging through irreversible damage to mitochondrial DNA (mtDNA). The mtDNA damage, which reduces the stabilization of adequate ATP supply during cardiac aging, disrupts the balance of cellular apoptosis, mitochondrial bioenergetics, and biogenesis. We highlight the specific mtDNA linked to mitochondrial biogenesis, oxidative metabolism, and the latent clinical utility of mtDNA in the aged heart

Molecular and Cellular Mechanisms of Cardiac Aging

Mitochondrial Dysfunction in Cardiac Aging

Mitochondrial Oxidative Metabolism and mtDNA Mutation in Cardiac Aging

Summary and Conclusions

Conflicts of Interest