Aging Dis. 2026 May 16. doi: 10.14336/AD.2026.0301. Online ahead of print.
ABSTRACT
The aging process is a major risk factor for numerous chronic diseases, and the progressive increase in global life expectancy has intensified the need to understand the molecular mechanisms underlying aging and age-related diseases. Volume-regulated anion channel (VRAC) plays a fundamental role in maintaining cellular homeostasis, among which leucine-rich repeat-containing protein 8A (LRRC8A) serves as the essential core subunit. Emerging evidence indicates that LRRC8A participates in diverse biological processes, including cell volume regulation, redox balance, metabolic homeostasis, inflammation and immune responses. Based on these mechanisms, LRRC8A may contribute to multiple aging-related processes, including inflammaging, immunosenescence and cellular senescence. Dysregulation of LRRC8A has been implicated in a variety of pathological conditions, including cardiovascular, neurodegenerative and metabolic diseases, many of which are strongly associated with aging. In this review, we summarize the current understanding of LRRC8A structure, biological functions, and signaling mechanisms, and discuss its emerging roles in aging and aging-related diseases. Furthermore, we discuss the therapeutic implications and translational constraints of LRRC8A modulation, emphasizing the need for tissue-specific, context-dependent, and aging-specific validation before clinical application.
PMID:42234967 | DOI:10.14336/AD.2026.0301