Regulation of Aging and Longevity by Ion Channels and Transporters

Abstract

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, Ca2+ 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.

Aging as a morphostasis defect: a developmental bioelectricity perspective

“…Recent research is starting to uncover the connections between aging, aging-related diseases, and bioelectricity primarily by recognizing the central role of ion channels [236,253,276,301]. Ion channels play a key role in maintaining physiological homeostasis by regulating membrane potential, signal transduction pathways and tissue information processing.…”

“…Lysosomal function plays a crucial role in regulating proteostasis, which is in turn modulated by ion channels [301]. Various stress-regulated ion channels have been identified [132,235], and damage to macromolecules may affect ion channels, leading to the disruption of the bioelectrical pattern necessary for maintaining the organism's structure.…”

“…Various stress-regulated ion channels have been identified [132,235], and damage to macromolecules may affect ion channels, leading to the disruption of the bioelectrical pattern necessary for maintaining the organism's structure. Ion channels and transporters are involved in regulating membrane excitability, Ca2+ homeostasis, mitochondrial and endolysosomal function, and the transduction of sensory signals, which in turn affect aging and longevity [301].…”