Grant: Project Grant

Aging is associated with an increase in body fat mass as well as a reduced thermogenic capacity, which both alter normal glucose and lipid metabolism. Previous discoveries in our lab have highlighted the possible role of a set of immune cells - B lymphocytes - that impair the normal response to insulin during life. We think that the changes in the activity of B cells are mediated in part by a gene named OcaB, which then provokes a negative action on fat tissues. However, how and when B cells impact fat tissues in old individuals is not known. This knowledge could prove to be ultimately clinically important since B cells produce antibodies that can specifically be blocked. In this grant, we wish to characterize the traffic and impact of B cells in adipose tissue of young versus old mice, how B cells sense their environment to modify their activity and produce more harmful antibodies in aging animals, and how this process ultimately has consequences for metabolism and inflammation. We will use an innovative methodology that allow to visualize tissue activity and senescence along the lifespan, which not only decreases the number of animals needed (and costs), but is very powerful because the effect of time (aging) can be observed within the same subject, allowing repeated measures factorial analyses. We will also try to demonstrate that pharmacological depletion of B cells improves healthspan in aged mice, which could be viewed as a first proof-of-principle for a potential development toward translational research.