Nature, published online 26 June 2013; doi:10.1038/nature12347

Senescent cells, or those that are no longer dividing, produce the senescence-associated secretory phenotype (SASP), marked by a cocktail of cytokines, chemokines and enzymes that has been linked to cancer risk in obesity. To understand the basis for this link, Yoshimoto et al. studied the impact of diet on cancer in mice and found that cancer-prone mice consuming a high-fat diet, but not a normal diet, developed hepatocellular carcinoma. The authors did find evidence of senescent cells in the liver, and mice lacking IL-1β, an upstream regulator of SASP induction, had smaller numbers and sizes of tumors compared to wild-type mice. As intestinal microbiota have been linked to obesity, the authors then demonstrated that antibiotic treatment led to decreased populations of senescent cells and carcinoma. The authors searched for a possible mediator of this interaction, identifying a single molecule—deoxycholic acid—as highly present in the serum metabolites of mice fed with high-fat but not a normal diet. Decreasing deoxycholic acid concentrations blocked formation of carcinomas and senescent cells, and, reciprocally, treatment with this molecule increased cancer formation in mice on a high-fat diet. These data led to a model where high fat consumption initiates deoxycholic acid production, which induces formation of senescent cells, with subsequent SASP inducing cancer.