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No use, distribution or reproduction is permitted which does not comply with these terms. Sirtuins belong to the class III family of NAD-dependent histone deacetylases HDAC and are involved in diverse physiological processes that range from regulation of metabolism and endocrine function to coordination of immunity and cellular responses to stress. Sirtuin-1 SIRT1 is the most well-studied family member and has been shown to be critically involved in epigenetics, immunology, and endocrinology. The versatile roles of SIRT1 include regulation of energy sensing metabolic homeostasis, deacetylation of histone and non-histone proteins in numerous tissues, neuro-endocrine regulation via stimulation of hypothalamus-pituitary axes, synthesis and maintenance of reproductive hormones via steroidogenesis, maintenance of innate and adaptive immune system via regulation of T- and B-cell maturation, chronic inflammation and autoimmune diseases.
In this review we aim to provide a broad overview on the role of SIRT1 particularly within the context of endocrinology and immunology. Early on the yeast counterpart Sir2 was shown to play a critical role in regulating DNA accessibility.
However, over the last decade our understanding of the function and targets of sirtuins has increased. SIRT1 is an evolutionary conserved enzyme whose presence can be traced to archaea. The number of sirtuin family members, varies across species and varies from a single family member in bacteria to seven in mammals Frye, ; Greiss and Gartner, Notably, human sirtuins are involved in a myriad of cellular processes that impact wide-ranging cellular processes from T cell differentiation to endocrine function.
As key regulators of homeostasis, dysregulated sirtuin activity is associated with a wide spectrum of diseases. Even though our understanding of their role in aging, cancer, metabolic syndrome, neuropathologies, and autoimmune diseases ADs is increasing, the complexity of their contribution continues to make it difficult to draw firm conclusions about causation or mechanisms.
