Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD+-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite func- tional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modu- lates genome stability, telomere integrity, transcription, and DNA repair. Its deficiency is associated with chronic inflammation, diabetes, cardiac hypertrophy, obesity, liver dysfunction, muscle/adipocyte dis- orders, and cancer. Besides, pieces of evidence showed that SIRT6 is a promoter of specific oncogenic pathways, thus disclosing its dual role regarding cancer development. Collectively, these findings sug- gest that multiple mechanisms, to date not entirely known, underlie the intriguing roles of SIRT6. Here we provide an overview of the current molecular mechanisms through which SIRT6 controls cancer and heart diseases, and describe its recent implications in the atherosclerotic plaque development.
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