Maestri E

Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction

Dietary restriction regimens, such as caloric restriction (CR), in the initiation and development of cancers has been studied using biological models and traditionally considers CR as anti-cancerogenic. However, the experimental, clinical facts and conclusions are controversial. CR-induced molecular and cellular mechanisms and pro-oncogenic pathways have not been systematically studied, leaving therapeutic benefits unclear. Here, using systems biology and deep data analysis approach, we study the CR-induced molecular pathway switches and cell-type context-specific responses known to underly early pre-malignant states in mouse and human mucosa. We identify the genes and energy-restricted networks associated with pre-malignant state metabolic reprogramming in normal stem cells and epithelial cell cycle activation, leading to telomere ends misbalance and immune response depletion. We define the changes in tumor suppressor and oncogenic pathways which may precede intestinal mucosa lesion development. This work will aid in the near future to define critical biomarkers for earlier detection and risk of adenomas and colorectal cancer.