Mitochondrial retrograde signaling as a therapeutic target for senescence-associated inflammation
With age, senescent cells accumulate in the body. These dysfunctional and abnormal cells contribute to disease in aged tissues through their inflammatory senescence-associated secretory phenotype (SASP). In preliminary studies, the SASP was shown to be dependent on pieces of nuclear DNA moving into the cytosol of senescent cells, termed cytosolic chromatin fragments (CCF). This phenomenon is dependent on abnormal mitochondrial function in senescent cells, although the mechanisms involved are incompletely understood.
In the proposed research, Dr. Karl Miller will investigate the relationship between mitochondrial function and CCF formation, as well as the causal role and mechanism of mitochondrial retrograde signaling in CCF formation. This research will allow for a better understanding of the SASP and could lead to therapies to reduce these inflammatory signals, ameliorate age-associated diseases, and promote healthy aging.
