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SRT2104 (GSK2245840) is a selective SIRT1 activator involved in the regulation of energy homeostasis. SIRT1, also known as NAD-dependent deacetylase sirtuin-1, is a member of the sirtuin family of proteins.

In vitro: In C2C12 myoblasts stably transfected with small hairpin RNA to knock-down SIRT1, SRT2104 increased AP activity, a marker for osteogenic differentiation. This effect was totally dependent on SIRT1 expression [1].

In vivo: In male C57BL/6J mice, administration of SRT2104 (100 mg/kg, p.o.) extended both mean and maximal lifespan of mice fed a standard diet, and enhanced bone mineral density, motor coordination, and insulin sensitivity and decreased inflammation. Short-term SRT2104 administration preserved bone and muscle mass in an experimental model of atrophy [1]. In Male N171-82Q HD mice with Huntington's disease, SRT2104 (diet containing 0.5% SRT2104) effectively penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival [2].

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