Racing toward its ultimate goal of being involved in every aspect of biology, the mammalian sirtuin SIRT1 has been the subject of a number of recent papers, each dealing with a different aspect of the protein’s role. (Abstracts are excerpted; ellipses, emphases, and interpolated commentary are mine.)
In energy metabolism and liver cirrhosis: Sirt1 is involved in energy metabolism: The role of chronic ethanol feeding and resveratrol, Oliva et al.:
These results support the concept that ethanol induces the Sirt1/PGC1α pathway of gene regulation and both naringin and resveratrol prevent the activation of this pathway by ethanol. However, resveratrol did not reduce the liver pathology caused by chronic ethanol feeding [In other words, it's probably not a good idea to get your resveratrol by drinking 1000 bottles of red wine a day.]
In diseases of protein aggregation: The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration, Chen et al. [a collaboration between the Lindquist and Guarente labs]:
We tested the role of SIRT1 in mediating the effects of CR in a mouse model of prion disease. … We report that the onset of prion disease is delayed by CR and in the SIRT1 KO mice fed ad libitum. CR exerts no further effect on the SIRT1 KO strain, suggesting the effects of CR and SIRT1 deletion are mechanistically coupled. In conjunction, SIRT1 is downregulated in certain brain regions of CR mice. … Surprisingly, CR greatly shortens the duration of clinical symptoms of prion disease and ultimately shortens lifespan of prion-inoculated mice in a manner that is independent of SIRT1. [i.e., CR isn't actually therapeutically beneficial since the mice die young.]
In inflammation, inflammaging, and HIV/AIDS: SIRT1 longevity factor suppresses NFκB -driven immune responses: regulation of aging via NFκB acetylation?, Salminen et al. (review):
HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NFκB complex. As a consequence, the transactivation efficiency of the NFκB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. … Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NFκB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.
In Notch regulation of stem cell aging: Sirt1, Notch and stem cell “age asymmetry”, Mantel et al. (review):
The protein-deacetylase, SIRT1, has received much attention because of its roles in oxygen metabolism, cellular stress response, aging, and has been investigated in various species and cell types including embryonic stem cells. However, there is a dearth of information on SIRT1 in adult stem cells, which have a pivotal role in adult aging processes. Here, we discuss the potential relationships between SIRT1 and the surface receptor protein, Notch, with stem cell self-renewal, asymmetric cell division, signaling, and stem cell aging.