BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer.

Aging is a significant risk factor for cancer which is due, in part, to heightened genomic instability. Mitotic surveillance proteins such as BubR1 play a pivotal role in ensuring accurate chromosomal segregation and preventing aneuploidy. BubR1 levels have been shown to naturally decline with age and its loss is associated with various age-related pathologies. Sirtuins, a class of NAD-dependent deacylases, are implicated in cancer and genomic instability. Among them, SIRT2 acts as an upstream regulator of BubR1, offering a critical pathway that can potentially mitigate age-related diseases, including cancer. In this review, we explore BubR1 as a key regulator of cellular processes crucial for aging-related phenotypes. We delve into the intricate mechanisms through which BubR1 influences genomic stability and cellular senescence. Moreover, we highlight the role of NAD and SIRT2 in modulating BubR1 expression and function, emphasizing its potential as a therapeutic target. The interaction between BubR1 and SIRT2 not only serves as a fundamental regulatory pathway in cellular homeostasis but also represents a promising avenue for developing targeted therapies against age-related diseases, particularly cancer.