Nuclear autophagy and senescence-associated inflammation
Protein abundance is balanced by synthesis and degradation. Imbalance of protein abundance is associated with aging. Autophagy, literally meaning self-eating, is a major degradation machinery in cells. Autophagy is a determinant of healthy versus unhealthy aging. For example, autophagy degrades toxic protein aggregates that promote disease, such as Alzheimer’s. Autophagy is thought to only degrade components in the cytoplasm. Recently, Dr. Dou’s lab reported the first component in cells’ nucleus that can be degraded by mammalian autophagy, namely the nuclear lamina, stimulating a new direction to study “nuclear autophagy”. This AFAR-supported project will identify what other nuclear proteins can be degraded by autophagy upon senescence, a form of cellular aging, and will further study a nuclear protein that regulates senescence-associated inflammation. This project will offer new knowledge to our understanding of nuclear protein abundance, and may find new ways to combat age-related inflammation.
