Mitochondrial dysfunction in the regulation of aging and aging-related diseases

Abstract Aging is an irreversible physiological process that progresses with age, leading to structural disorders and dysfunctions of organs, thereby increasing the risk of chronic diseases such as neurodegenerative diseases, diabetes, hypertension, and cancer. Both organismal and cellular aging are...

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Main Authors: Xianhong Zhang, Yue Gao, Siyu zhang, Yiqi Wang, Xinke Pei, Yufei Chen, Jinhui Zhang, Yichen Zhang, Yitian Du, Shauilin Hao, Yujiong Wang, Ting Ni
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-025-02308-7
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author Xianhong Zhang
Yue Gao
Siyu zhang
Yiqi Wang
Xinke Pei
Yufei Chen
Jinhui Zhang
Yichen Zhang
Yitian Du
Shauilin Hao
Yujiong Wang
Ting Ni
author_facet Xianhong Zhang
Yue Gao
Siyu zhang
Yiqi Wang
Xinke Pei
Yufei Chen
Jinhui Zhang
Yichen Zhang
Yitian Du
Shauilin Hao
Yujiong Wang
Ting Ni
author_sort Xianhong Zhang
collection DOAJ
description Abstract Aging is an irreversible physiological process that progresses with age, leading to structural disorders and dysfunctions of organs, thereby increasing the risk of chronic diseases such as neurodegenerative diseases, diabetes, hypertension, and cancer. Both organismal and cellular aging are accompanied by the accumulation of damaged organelles and macromolecules, which not only disrupt the metabolic homeostasis of the organism but also trigger the immune response required for physiological repair. Therefore, metabolic remodeling or chronic inflammation induced by damaged tissues, cells, or biomolecules is considered a critical biological factor in the organismal aging process. Notably, mitochondria are essential bioenergetic organelles that regulate both catabolism and anabolism and can respond to specific energy demands and growth repair needs. Additionally, mitochondrial components and metabolites can regulate cellular processes through damage-associated molecular patterns (DAMPs) and participate in inflammatory responses. Furthermore, the accumulation of prolonged, low-grade chronic inflammation can induce immune cell senescence and disrupt immune system function, thereby establishing a vicious cycle of mitochondrial dysfunction, inflammation, and senescence. In this review, we first outline the basic structure of mitochondria and their essential biological functions in cells. We then focus on the effects of mitochondrial metabolites, metabolic remodeling, chronic inflammation, and immune responsesthat are regulated by mitochondrial stress signaling in cellular senescence. Finally, we analyze the various inflammatory responses, metabolites, and the senescence-associated secretory phenotypes (SASP) mediated by mitochondrial dysfunction and their role in senescence-related diseases. Additionally, we analyze the crosstalk between mitochondrial dysfunction-mediated inflammation, metabolites, the SASP, and cellular senescence in age-related diseases. Finally, we propose potential strategies for targeting mitochondria to regulate metabolic remodeling or chronic inflammation through interventions such as dietary restriction or exercise, with the aim of delaying senescence. This reviewprovide a theoretical foundation for organismal antiaging strategies.
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spelling doaj-art-1aadabe34b8a4efc950888c38d59cddc2025-08-20T02:10:34ZengBMCCell Communication and Signaling1478-811X2025-06-0123113510.1186/s12964-025-02308-7Mitochondrial dysfunction in the regulation of aging and aging-related diseasesXianhong Zhang0Yue Gao1Siyu zhang2Yiqi Wang3Xinke Pei4Yufei Chen5Jinhui Zhang6Yichen Zhang7Yitian Du8Shauilin Hao9Yujiong Wang10Ting Ni11State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityKey Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, School of Life Sciences, Ningxia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityKey Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, School of Life Sciences, Ningxia UniversityState Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, School of Life Sciences, Inner Mongolia UniversityAbstract Aging is an irreversible physiological process that progresses with age, leading to structural disorders and dysfunctions of organs, thereby increasing the risk of chronic diseases such as neurodegenerative diseases, diabetes, hypertension, and cancer. Both organismal and cellular aging are accompanied by the accumulation of damaged organelles and macromolecules, which not only disrupt the metabolic homeostasis of the organism but also trigger the immune response required for physiological repair. Therefore, metabolic remodeling or chronic inflammation induced by damaged tissues, cells, or biomolecules is considered a critical biological factor in the organismal aging process. Notably, mitochondria are essential bioenergetic organelles that regulate both catabolism and anabolism and can respond to specific energy demands and growth repair needs. Additionally, mitochondrial components and metabolites can regulate cellular processes through damage-associated molecular patterns (DAMPs) and participate in inflammatory responses. Furthermore, the accumulation of prolonged, low-grade chronic inflammation can induce immune cell senescence and disrupt immune system function, thereby establishing a vicious cycle of mitochondrial dysfunction, inflammation, and senescence. In this review, we first outline the basic structure of mitochondria and their essential biological functions in cells. We then focus on the effects of mitochondrial metabolites, metabolic remodeling, chronic inflammation, and immune responsesthat are regulated by mitochondrial stress signaling in cellular senescence. Finally, we analyze the various inflammatory responses, metabolites, and the senescence-associated secretory phenotypes (SASP) mediated by mitochondrial dysfunction and their role in senescence-related diseases. Additionally, we analyze the crosstalk between mitochondrial dysfunction-mediated inflammation, metabolites, the SASP, and cellular senescence in age-related diseases. Finally, we propose potential strategies for targeting mitochondria to regulate metabolic remodeling or chronic inflammation through interventions such as dietary restriction or exercise, with the aim of delaying senescence. This reviewprovide a theoretical foundation for organismal antiaging strategies.https://doi.org/10.1186/s12964-025-02308-7MitochondriaCellular senescenceMetabolic remodellingChronic inflammationAging-related diseases
spellingShingle Xianhong Zhang
Yue Gao
Siyu zhang
Yiqi Wang
Xinke Pei
Yufei Chen
Jinhui Zhang
Yichen Zhang
Yitian Du
Shauilin Hao
Yujiong Wang
Ting Ni
Mitochondrial dysfunction in the regulation of aging and aging-related diseases
Cell Communication and Signaling
Mitochondria
Cellular senescence
Metabolic remodelling
Chronic inflammation
Aging-related diseases
title Mitochondrial dysfunction in the regulation of aging and aging-related diseases
title_full Mitochondrial dysfunction in the regulation of aging and aging-related diseases
title_fullStr Mitochondrial dysfunction in the regulation of aging and aging-related diseases
title_full_unstemmed Mitochondrial dysfunction in the regulation of aging and aging-related diseases
title_short Mitochondrial dysfunction in the regulation of aging and aging-related diseases
title_sort mitochondrial dysfunction in the regulation of aging and aging related diseases
topic Mitochondria
Cellular senescence
Metabolic remodelling
Chronic inflammation
Aging-related diseases
url https://doi.org/10.1186/s12964-025-02308-7
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