Ageing Research Reviews · Jun 24, 2026
Ubiquitin-specific proteases in cardiovascular disease particularly in aging: mechanisms and therapeutic prospects
By Ma D, Wang Z, Ji C et al.
Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide. The ubiquitin proteasome system (UPS) is essential for maintaining intracellular protein homeostasis, and growing evidence indicates that its dysregulation critically contributes to the onset and progression of various CVDs, particularly in the context of aging. Among these, ubiquitin-specific proteases (USPs) have emerged as promising therapeutic targets, but their precise roles and regulatory mechanisms in cardiovascular and aging pathophysiology have not been fully elucidated. This review systematically examines the molecular functions of individual USPs and their functional interactions in the cardiovascular system and aging, with an emphasis on their involvement in inflammatory responses, metabolic dysregulation, and mitochondrial homeostasis. We also discuss the translational potential and challenges of USP-directed therapeutic strategy, and offer a new perspective on the development of future cardiovascular treatments targeting this family of enzymes.