Nutrition can have profound effects on aging and age-related pathologies including cancer. As such, studies of fasting (the complete withdrawal of food) and dietary restriction (DR, generally described as a 20- 40% reduction in calories) have greatly contributed to the understanding of the relationship between nutrients, cellular aging, cancerogenesis and cancer cell survival. Our findings in yeast indicated that starvation decreases age-dependent mutations whereas our mouse xenograft tumor models indicate that fasting alone can be as effective as chemotherapy drugs in delaying the progression of certain tumor types, in part through the reduction of extracellular glucose and IGF-1 concentration/signaling. Here, we developed a fasting mimicking/enhancing diet (FMD) and tested its effects on cancerogenesis. In a cohort of female C57Bl6 mice, bi-monthly 4 day FMD feeding cycles followed by normal food intake, significantly improved survival in mice without causing excessive weight loss. Mice in the FMD cohort had a significantly reduced lifelong cancer incidence rate. Lymphoma was the most common cause of morbidity/mortality and affected ∼67% in the ad lib fed control group but only ∼40% of the FMD fed mice. In both cohorts lymphomas contributed to the great majority of all neoplasms found. Neoplasms were found in animals in the ad lib fed cohort starting 5 months after onset of our study, whereas no tumors occurred in the first 8 months in the FMD cohort. Furthermore, the FMD caused a shift from the presence of tumors in multiple organs (≥3) to tumors being either absent or present in 2 or less sites, thus indicating a potential shift to the development of benign tumors in the FMD group. In summary, the periodic FMD cycles had a significant impact on the development of cancer while allowing the preservation of lean body mass and animal weight until old age and extending longevity.
Citation Format: Sebastian Brandhorst, Min Wei, Gerrardo Navarre, Louis Dubeau, Peter Conti, Todd Morgan, Valter D. Longo. Periodic fasting mimicking diet started late in life reduces and delays carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4120. doi:10.1158/1538-7445.AM2014-4120
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