Telomere length induced changes in gene expression: mechanistic role in metabolism and aging
Description: Telomere length is involved in the regulation of gene expression, through telomere position effects (TPE). Traditional TPE is a phenomenon where when telomeres are long, they are heterochromatic and thus genes nearby are silenced (not expressed), and when telomeres shorten the spreading of heterochromatin results in the expression (aberrant in some cases) of genes near telomeres. In addition, telomeres form chromatin loops that are dependent on the length of telomeres and make contacts with enhancer and repressor regions leading to altered genes expression in a non-linear fashion. Since many human genes including microRNAs, splicing factors, and genes in that regulate metabolism, are within 10Mb of chromosome ends, it is likely that telomere position effects over long distances (TPE-OLD) plays a role in aging and disease risk. Initial studies will focus on how splicing factors/RNA binding proteins and non-coding RNAs are regulated by telomere length and in turn how the mis-expression of these factors/RNAs alters metabolism of various cell types, such as, immune cells, mesenchymal stem cells, muscle cells and epithelial cells. The major questions we would be trying to answer are how telomere length plays a role in disease progression processes such as immune-senescence, type II diabetes, and cancer progression. Ultimately, we would try to reverse the effects of short telomeres on gene expression of these important splicing factors/non-coding RNAs by developing interventions to maintain or slow the rate of telomere shortening by enhancing telomerase biogenesis via increased exercise, healthy diet, or therapeutics.