We know that sirtuins (especially SIRT1) promote longevity, but every so often we hear of a potentially negative consequence of these molecules (e.g., see the second portion of An unSIRTain role in neurodegeneration, in which we learned that SIRT2 inhibition can slow the onset of Parkinson’s disease in a rodent model).

Adding to the admittedly short list of potential downsides of sirtuin activity, Huffman et al. report that SIRT1 expression is high in prostate tumor cells, suggesting that the protein may have a role as a tumor promoter:

SIRT1 Is Significantly Elevated in Mouse and Human Prostate Cancer

… To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 … Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. … [W]hen examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. … Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. … SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.

The data are circumstantial: the authors demonstrate a correlation but perform no interventional experiments (e.g., expressing SIRT1 in otherwise non-neoplastic cells) that might address the question of causation. One could also argue that there are a host of genes that are upregulated in cancer cells as a secondary consequence of the tremendous stress these cells have to deal with (genomic, protein folding, etc.), and certainly no reasonable person would argue that e.g. heat shock proteins are tumor promoter.

So for the moment, it’s merely a case of seeing a good friend in a bad neighborhood and wondering what the heck he’s doing there. In order to learn whether SIRT1 is instigating or merely slumming — as the old saying goes, further experiments are required.