Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

We have long known that women live longer than men, and that the biological aging process differs between the sexes, not just in humans, but in many animals. However, we have very little understanding of why women age more slowly, nor what this means for treating patients in a sex-appropriate way as they age. Recent research in our lab suggests a way forward: we have developed the first reliable way to measure "physiological dysregulation," the way that our bodies slowly lose the ability to control the many functions necessary to sustain life. We have shown that physiological dysregulation changes differently with age in men and women. Here, we propose to study in detail how physiological dysregulation happens in men and women. Does the immune system become dysregulated faster in one sex than the other? Do changes in certain types of dysregulation increase the risk of chronic diseases more in one sex than the other? The answers to questions such as these will paint a portrait of the aging process in each sex, and suggest clinical directions that will tailor treatment of aging patients to the way their sex ages. To do this, we use innovative statistical methods we developed applied to large datasets of biomarkers (cholesterol, blood sugar, anemia, etc.) followed over time in thousands of patients. We will also confirm our results in seven primate species in order to establish how biologically universal any differences are. These results will advance fundamental biological knowledge of how aging differs between the sexes, and will also create a foundation for clinical interventions.