Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence.

Yun Haeng Lee,Haneur Lee,Sang Chul Park,Eun Seon Song,Junghyun Joo,Sekyung Oh,Myeong Uk Kuk,Hyung Wook Kwon,Joon Tae Park,Ji Yun Park

doi:10.3390/cells10113003

Yun Haeng Lee, Haneur Lee + Show 8 more

Open Access

https://doi.org/10.3390/cells10113003

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Journal: Cells	Publication Date: Nov 3, 2021
Citations: 24	License type: CC BY 4.0

Affiliation: Incheon National University, Chonnam National University

Abstract

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases. In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.

Highlights

Published: 3 November 2021Senescence is characterized by a condition in which somatic cells lose their capacity to proliferate after a limited number of mitotic divisions [1]
The role of mitochondrial metabolic reprogramming in senescence has been analyzed and reviewed by several researchers
The importance of mitochondrial metabolism in senescence has been discussed, it has been limited to its role in endothelial cells (ECs)

Summary

Introduction

Senescence is characterized by a condition in which somatic cells lose their capacity to proliferate after a limited number of mitotic divisions [1]. Mitochondria undergo structural changes associated with significant increases in size and volume [2]. Changes in mitochondrial metabolism occur during senescence, demonstrating that senescent fibroblasts rely less on OXPHOS but more on glycolysis as a source of energy [5]. This finding is supported by observations that alterations in mitochondrial metabolism contribute to premature reductions in organ function [6]; the underlying mechanisms for reprogramming altered. Basic knowledge of mitochondrial metabolic reprogramming and mechanism-based strategies for regulating mitochondrial metabolism are needed. Based on previous and recent findings, we provide new insights into the crosstalk between mitochondrial metabolism and senescence, and propose mitochondrial metabolic reprogramming as a therapeutic target for aging and age-related diseases

Mitochondrial Alterations Associated with Senescence

Alterations in Mitochondrial Metabolism Associated with Senescence

Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence

Findings

Conclusions and Perspectives