The road to your heart (and brain and muscles) is through your stomach

Why do all parts of an organism age at the same rate? It has been hypothesized that a diffusible factor (e.g., a hormone signal) synchronizes the progress of aging throughout the body. Now, from Coleen Murphy, we have experimental evidence that this is exactly what is happening in the worm C. elegans: DAF-16 activity in the intestine results in synthesis of an insulin-like hormone, INS-7, which communicates with tissues outside the gut and stimulates increased DAF-16 activity elsewhere in the body. From Murphy et al:

Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans

How are the rates of aging of different tissues coordinated? In Caenorhabditis elegans, decreasing insulin/IGF-1 signaling extends lifespan by activating the transcription factor DAF-16/FOXO. If DAF-16 levels are experimentally increased in one tissue, such as the intestine, DAF-16 activity in other tissues rises. Here we test the hypothesis that this “FOXO-to-FOXO” signaling occurs via feedback regulation of ins-7 insulin gene expression. We find that DAF-16 regulates ins-7 expression in the intestine, and that preventing this regulation blocks FOXO-to-FOXO signaling from the intestine to other tissues. Our findings show that feedback regulation of insulin gene expression coordinates DAF-16 activity among the tissues, and they establish the intestine, which is the animal’s entire endoderm, as an important insulin-signaling center.

The significance of the intestine in this story is especially intriguing given last year’s report that pha-4, a gene involved in foregut development, is essential for the longevity-enhancement benefits of calorie restriction.