Enhancing healthy aging with small molecules: A mitochondrial perspective

IF 10.9 1区 医学 Q1 CHEMISTRY, MEDICINAL Medicinal Research Reviews Pub Date : 2024-03-14 DOI:10.1002/med.22034
Xiujiao Qin, Hongyuan Li, Huiying Zhao, Le Fang, Xiaohui Wang
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Abstract

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha-lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5′-monophosphate-activated protein kinase activators, and compounds like metformin and mitochondria-targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age-related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge.

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用小分子促进健康老龄化:线粒体视角
为了在衰老过程中增进健康,人们开始探索各种策略,以减少衰老过程中出现的衰退现象。这一探索的一个关键领域是线粒体功能障碍的管理,这是衰老的一个显著特征。本综述揭示了小分子在促进健康老龄化方面发挥的关键作用,特别是通过影响线粒体功能发挥的作用。线粒体氧化损伤是衰老的一个重要方面,通过辅酶 Q10、α-硫辛酸和各种抗氧化剂等干预措施,有可能减轻线粒体氧化损伤。此外,本综述还讨论了增强线粒体蛋白稳态的方法,强调了线粒体未折叠蛋白反应诱导剂(如强力霉素)和影响有丝分裂的药物(如尿磷脂 A、亚精胺、曲哈糖和牛磺酸)的重要性,这些药物对维持蛋白质质量控制至关重要。同样重要的是调节线粒体能量产生的方法,其中包括烟酰胺腺嘌呤二核苷酸促进剂、5'-单磷酸腺苷激活蛋白激酶激活剂,以及二甲双胍和线粒体靶向他莫昔芬等可增强代谢功能的化合物。此外,综述还深入探讨了促进线粒体生物生成的新兴策略。总之,这些干预措施为解决与年龄相关的线粒体退化问题提供了一条大有可为的途径,从而为开发创新的治疗方法以应对这一广泛的挑战创造了条件。
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来源期刊
CiteScore
29.30
自引率
0.00%
发文量
52
审稿时长
2 months
期刊介绍: Medicinal Research Reviews is dedicated to publishing timely and critical reviews, as well as opinion-based articles, covering a broad spectrum of topics related to medicinal research. These contributions are authored by individuals who have made significant advancements in the field. Encompassing a wide range of subjects, suitable topics include, but are not limited to, the underlying pathophysiology of crucial diseases and disease vectors, therapeutic approaches for diverse medical conditions, properties of molecular targets for therapeutic agents, innovative methodologies facilitating therapy discovery, genomics and proteomics, structure-activity correlations of drug series, development of new imaging and diagnostic tools, drug metabolism, drug delivery, and comprehensive examinations of the chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of significant drugs.
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