Sirtuins and their role in ovarian aging-related fibrosis predisposing to ovarian cancer.

Abstract

The pursuit of understanding early genetic or protein markers for ovarian aging has garnered considerable attention in the realm of reproductive medicine. Sirtuins (SIRTs) are a group of proteins that are NAD⁺-dependent, and thanks to their properties, they are able to change the acetylation profile of proteins and post-translationally modify their functions, too. Previous research provided evidence that SIRTs influence fibrosis levels in several organs. With regard to ovaries, fibrosis is one of the features of aged ovaries and also creates a metastasis-friendly environment, thus can also be a seedbed for the development of primary cancerous lesions. Ovarian cancer remains a formidable challenge in oncology due to its high prevalence, insidious onset, and frequent recurrence. Noteworthy, ovarian cancer is the seventh most common cancer among women and the eighth leading cause of cancer death worldwide. Ovarian fibrosis runs concurrently with the activation of TGF-β/Smads signaling, as well as inflammasome (NLRP3), nuclear factor kB (NFkB) and forkhead box O (FOXO) attenuation. Reduced levels of certain sirtuins resulting from decreased nicotinamide adenine dinucleotide (NAD + ) may underlie the dysregulation of the aforementioned signaling pathways and therefore represent a potential therapeutic target. This review elucidates the role of SIRTs in ovarian aging-related fibrosis as a process that predisposes to tumorigenesis.