Late-life short-term dietary restriction ameliorates intestinal stem cell function and impacts intestinal stem cell DNA methylation

Aging reduces the function of intestinal stem cells (ISCs) and dietary restriction (DR) has been shown to improve ISC function in young mice. However, there are no studies to-date that has evaluated the effect of short-term DR (stDR) implemented late-in-life on ISC function. Data from our laboratory shows for the first time that stDR can ameliorate the age-related decline in ISC function by in-vitro enteroid forming assay. Transcriptomic analysis of the Lgr5+ ISCs identified genes not commonly known for ISC function but showed a robust change with age which were reversed by stDR. Evaluation of the methylation status of selected genes (Slc28a3, Ly9, Cd2, Platr4) showed association between changes in 5mCG levels in the cis-acting regions of the genes and their expression. Our data suggest a potential role for DNA methylation in stDRs effect on ISC function.