Significance:
Sirtuins are
NAD+-dependent histone deacetylases regulating important processes in cellular biology such as
inflammation, metabolism, oxidative stress, and apoptosis. Recent Advances: Despite initially being discovered to regulate transcription and life span via
histone deacetylase activities, emerging data continually uncover new targets and propose additional roles. Due to the outstanding importance of the
sirtuins in the control of the inflammatory response, their roles in the pathogenesis of several inflammatory-based diseases have become an area of intense research. Although
sirtuins have been traditionally regarded as anti-inflammatory players, several recent findings suggest that their role in
inflammation is complex and that in some cases
sirtuins can indeed promote
inflammation. Critical Issues: In this article, we provide an update on the latest findings concerning the new mechanisms of action and concepts about the role of
sirtuins during
inflammation. We focus on the impact that inflammatory-based processes exert on the liver, adipose tissue, and nervous system as well as on macrophage function and activation. Also, we discuss available data pointing to the dual role that, in particular contexts,
sirtuins may have on
inflammation control. Future Directions: Since the knowledge of
sirtuin impact on metabolism is continually expanding, new venues of research arise. Besides become being regarded as candidates of therapeutic targets, posttranscriptional control of
sirtuin expression by means of
microRNAs challenges our traditional concepts of
sirtuin regulation; importantly, the emerging role of NAD+ metabolism in aging and longevity has added a new dimension to the interest in
sirtuin function.