Editors' ChoiceMetabolism

High Steaks for Cancer and Aging

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Science Translational Medicine  19 Mar 2014:
Vol. 6, Issue 228, pp. 228ec49
DOI: 10.1126/scitranslmed.3008866

By 2030, nearly 20% of the total U.S. population will be 65 years of age or older. Thus, there is a demand for new advances that reduce age-related diseases and improve quality of life. Over the past several decades, researchers have found that restricting calories by 30 to 50% increases life span in many species, in part by reducing growth hormone and insulin/insulin growth factor-1 (IGF-1) signaling. Previously, Longo and colleagues monitored Ecuadorian individuals with growth hormone receptor (GHR) mutations and reduced IGF-1 levels and discovered that these individuals have dramatically reduced rates of cancer and diabetes. Because protein restriction is known to reduce IGF-1, Longo and colleagues reasoned that dietary protein intake might influence the risk for cancer and diabetes during aging and tested this hypothesis in a new study.

The authors analyzed data from a dietary survey of 6381 U.S. men and women over the age of 50. Subjects were divided into high (20% or more calories from protein), moderate (10 to 19%), and low (<10%) protein intake groups. By linking the data with resources available from the National Death Index, the authors were able to define the timing and cause of death for participants. Remarkably, individuals in the high-protein group had a 73-fold increased risk for diabetes mortality. Further, subjects in the high-protein group between ages 50 and 65 had a 74% increased risk for all-cause mortality and a fourfold increased risk for cancer mortality. Subjects who consumed a moderate amount of protein had a threefold higher cancer mortality risk. In a random sampling of 2253 individuals, IGF-1 levels were positively associated with protein intake, and the authors were able to predict that for every 10 ng/ml increase in IGF-1, the mortality risk for cancer increases by 9%. To verify the link between protein intake, IGF-1, and cancer risk, the authors implanted tumor cells into mice on high- or low-protein diets and found that serum IGF-1 concentrations were 35% higher—and that tumors grew faster and 78% larger—in animals on the high-protein diets. When tumor cells were implanted into GHR/IGF-1–deficient mice, tumor progression was inhibited, demonstrating a role for endogenous GHR/IGF-1 signaling in tumor growth. Last, the authors found that at later stages of life (66 years and older), increased protein intake was beneficial and significantly reduced all-cause and cancer-related mortality.

This study demonstrates that high-protein intake at younger ages is associated with a significantly increased risk for diabetes and cancer, which is timely given the current popularity of high-protein diets (“Paleo” diets and others). The study also suggests that dietary requirements change with age. Future studies focused on understanding the interaction between dietary and genetic risk factors will help to further tailor nutrition for individuals at different ages.

M. E. Levine et al., Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 19, 407–417 (2014). [Abstract]

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