SIRT1 reduces lactate production by modifying PKM2 to help prevent early ovarian failure

SIRT1 expression was markedly downregulated in patients with premature ovarian insufficiency (POI).

• Downregulation of SIRT1 is associated with increased acetylation of pyruvate kinase M2 (PKM2) and elevated lactate levels.
• Restoration of SIRT1 activity through specific interventions improved follicular development and reduced cell death in granulosa cells.
• Serum levels of anti-Müllerian hormone and follicle-stimulating hormone were normalized following the restoration of SIRT1 function.
• SIRT1 directly interacts with PKM2, leading to decreased lactate production and maintenance of ovarian function.
• Targeting the SIRT1-PKM2-lactate metabolic pathway could offer a potential therapeutic approach for managing POI.

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