Description: Telomere length shortens with age. Telomere shortening over time or progressive telomere shortening leads to senescence, apoptosis, and potentially oncogenic transformation of cells, which in turn shortens the health span and lifespan of individuals. Certain lifestyle factors can alter the rate of telomere shortening, for instance, the rate of telomere shortening is slowed down by maintaining a moderate level of physical activity. Diseases of inactivity such as insulin resistance, chronic inflammation, and altered endocrine signaling may increase the rate of telomere shortening and increase the risk of cancer. Thus, this project broadly aims to understand the connections between lifestyle factors (diet and exercise), the regulation of telomere length, and how this alters the risk for certain cancers. Initial studies will focus on the mechanisms of how exercise and diet influence telomerase activity and telomere length regulating proteins, particularly focusing on the signaling mechanisms that result in enhanced telomere protection and maintenance (DNA repair, fidelity of DNA replication, etc.) and how this affords genome stability and reduced cancer risk. In particular we will focus on how somatotrophic signaling results in altered chromatin, epigenetics, transcriptional factor recruitment, and splicing of TERT/human TERT, following diet and exercise interventions to slow the rate of telomere shortening. To perform this research, we will use a combination of human participants, rodent models and human/mouse tissue culture models. The ultimate goal of this research will be to define the molecules that are triggered by healthy lifestyle choices that result in enhanced genome stability (i.e., telomere maintenance) and develop therapeutics to target these molecules to treat diseases of short telomeres and reduce the risk of certain cancer types.