Aging is the greatest risk factor for many chronic diseases including cancer, neurodegeneration, diabetes, and heart disease. Currently, roughly half of the VA population is aged 65+ years, and in the next ten years, more than 3 million of these veterans are expected to be over 75. Thus, studying genes that regulate aging and aging-associated pathologies is critically important for biomedical advancements to benefit veterans’ health. This research program investigates two such genes, SIRT6 and SIRT7, which are “master regulators” of many changes in aging tissues, such as DNA damage, metabolic and oxidative stress, cellular senescence, and inflammation. Our projects study how decreased activity of these genes may contribute to pathologies in cardiovascular and liver disease, diabetes, obesity, and many cancers, and how activating these genes could protect against these pathologies. By identifying pathways that can be targeted for therapy, this research can directly impact the health of the Veteran population. .