Anticancer mechanisms in a long-lived rodent, the naked mole-rat

2009 senior Scholar Award in aging

The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, the naked mole-rat has extraordinary resistance to cancer as tumors have never been observed in these rodents. The mechanism for cancer resistance in the naked mole-rat is unknown. The goal of our research is to understand the mechanisms behind the extraordinary resistance to cancer in the naked mole-rat. We found that naked mole-rat fibroblasts display hypersensitivity to contact inhibition, a phenomenon we termed ìearly contact inhibitionî. Contact inhibition is a key anti-cancer mechanism that arrests cell division when cells reach high density. Therefore, hypersensitivity of naked mole-rat cells to contact inhibition is likely to contribute to cancer resistance of this animal. Our specific aims are: (1) to characterize early contact inhibition in various cell types in vitro, and examine the impact of early contact inhibition on normal tissue architecture in vivo; (2) identify signaling pathways controlling early contact inhibition; (3) determine minimal requirements for malignant transformation of naked mole-rat cells. This project will provide insight into anti-cancer mechanisms that evolved in this exceptionally long-lived mammal. Our hope is that investigation of long-lived mammalian species will unravel mechanisms of cancer resistance and longevity that will be applied to extend human lifespan.