Mitochondria: The master regulator of aging

Abstract

Mitochondria are ATP-producing organelles in eukaryotic organisms that serve as the cell’s power plants. Besides, mitochondria are integral to regulating cellular homeostasis and metabolism as a result of their essential roles in reactive oxygen species (ROS) production, bioenergetics, catabolism and anabolism, heme and iron-sulfur biosynthesis, iron and calcium homeostasis, apoptosis and signal transduction, as well as immunity and inflammation. It is well accepted that mitochondria are evolutionarily derived from endosymbiotic alphaproteobacteria within eukaryotic cells adapted for effective energy transduction. Although most of the mitochondrial DNA (mtDNA) is thought to have been transported to the eukaryotic nucleus during evolution, mitochondria may have preserved protein-coding genes within their own DNA. Accumulating data show that a progressive decline of mitochondria regulates aging. The present review aims to outline the role of mitochondria in various aspects of aging, including unfolded protein response, generation of ROS, and the contribution of somatic mtDNA mutations as well as inflammation in aging. Moreover, we propose mitochondria-targeted nanoparticles and mitochondrial genome editing as novel tools to modify mitochondrial genome aberrations.