Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center (UTHealth-Houston), Houston, TX 77030, USA.
Graduate Programs in Neuroscience and Biochemistry and Cell Biology, MD Anderson Cancer Center and UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
Cells. 2022 Mar 31;11(7):1180. doi: 10.3390/cells11071180.
Despite significant advances in our understanding of the mechanisms that underlie age-related physiological decline, our ability to translate these insights into actionable strategies to extend human healthspan has been limited. One of the major reasons for the existence of this barrier is that with a few important exceptions, many of the proteins that mediate aging have proven to be undruggable. The argument put forth here is that the amenability of ion channels and transporters to pharmacological manipulation could be leveraged to develop novel therapeutic strategies to combat aging. This review delves into the established roles for ion channels and transporters in the regulation of aging and longevity via their influence on membrane excitability, Ca homeostasis, mitochondrial and endolysosomal function, and the transduction of sensory stimuli. The goal is to provide the reader with an understanding of emergent themes, and prompt further investigation into how the activities of ion channels and transporters sculpt the trajectories of cellular and organismal aging.
尽管我们在理解导致与年龄相关的生理衰退的机制方面取得了重大进展,但将这些见解转化为可操作的策略来延长人类健康寿命的能力却受到了限制。造成这种障碍的一个主要原因是,除了少数几个重要的例外,许多介导衰老的蛋白质已被证明是不可成药的。这里提出的论点是,离子通道和转运蛋白对药物处理的易感性可以被利用来开发新的治疗策略来对抗衰老。本综述深入探讨了离子通道和转运体在通过影响膜兴奋性、Ca 稳态、线粒体和内溶酶体功能以及感觉刺激转导来调节衰老和长寿方面的既定作用。其目的是为读者提供对新兴主题的理解,并促使进一步研究离子通道和转运体的活性如何塑造细胞和机体衰老的轨迹。