{"title":"Targeting organ-specific mitochondrial dysfunction to improve biological aging","authors":"","doi":"10.1016/j.pharmthera.2024.108710","DOIUrl":null,"url":null,"abstract":"<div><p>In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function.</p><p>The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics.</p><p>We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues.</p><p>In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":null,"pages":null},"PeriodicalIF":12.0000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016372582400130X/pdfft?md5=8f87dab5dd66f3b5f2112c8e90a66766&pid=1-s2.0-S016372582400130X-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016372582400130X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function.
The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics.
We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues.
In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.
在老龄化社会中,揭示新的抗衰老战略以预防和抗击与衰老有关的疾病至关重要。线粒体是产生 ATP 的主要场所,也是细胞程序性死亡的关键调节器。因此,这些高度动态的细胞器在维持组织功能方面发挥着核心作用,而线粒体功能障碍是与年龄相关的细胞稳态和器官功能逐渐衰退的关键因素。本综述探讨了了解线粒体功能障碍与器官特异性衰老之间相互作用的最新进展。通过探讨线粒体 DNA 的作用、活性氧平衡、代谢活动、损伤相关分子模式、生物生成、周转和动力学,我们剖析了线粒体损伤与器官功能衰退相关的分子机制。我们还重点介绍了临床前和临床试验中有望恢复线粒体功能的新兴治疗策略,如抗氧化剂、线粒体生物生成刺激剂以及线粒体更替和动态调节剂。此外,我们还讨论了与使用这些干预措施相关的潜在益处和挑战,并强调鉴于不同组织线粒体的独特性,有必要采用针对特定器官的方法。总之,本综述强调了解决线粒体功能障碍以缓解器官特异性衰老的治疗潜力,重点关注皮肤、肝脏、肺、大脑、骨骼肌和肺,以及生殖、免疫和心血管系统。在全面了解线粒体多方面作用的基础上,可以开发和优化创新的治疗策略,以对抗生物衰老,促进不同器官系统的健康衰老。
期刊介绍:
Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.