Grant: Travel Awards - Institute Community Support

In the last few years, researchers were surprised to find that we can detect a large proportion of mutated blood cells in >10% of people >65 years old. These people have an increased risk of developing cardiovascular issues, diabetes, blood cancer and of overall death. The mutated blood cell population arises from a stem cell (in the bone marrow) that is mutated in a cancer-associated gene. This condition is called Clonal Hematopoiesis of Indeterminate Potential ("CHIP"). Researchers suspect that inflammation may help this mutated stem cell to multiply and produce a large proportion of blood cells, or that the mutated cells are more inflammatory ("pro-inflammatory"). The mutated blood cells that circulate in the body may then exert damage. The hypothesis of my current work is that these mutated cells are pro-inflammatory, and that people with these mutated cells (people with CHIP) have poorer health. To test this idea, I used DNA sequencing to detect mutations in the blood of 30 otherwise healthy people >65 years old. We then analyzed which genes are getting made into proteins (RNA sequencing) in these blood samples, which tells us how the cells may be malfunctioning. Genes that are involved in a specific blood cell type (in neutrophils) that enable the cell to destroy dangerous materials are highly abundant in people with CHIP. This suggests that people with CHIP have overly active neutrophils, and this may relate to their poorer overall health. Additionally, people with larger mutated cell populations have poorer functioning than people without CHIP (as measured by an ECOG score). My work builds toward improving the quality of life of older adults. If we can counter the pro-inflammatory nature of neutrophils in people with CHIP, perhaps we can mitigate the ill health that is associated with CHIP. Monitoring for CHIP and future preventative medicine may lead to improvements in individuals' quality of life and the healthcare burden for the aging population.