The Proteomic Landscape of the Human Nucleolus during Senescence

Mayflies can live for 24 hours. Giant tortoises can live for almost 200 years. As an organism ages, its tissues and organs decline, leading to a diminishing capacity to respond to stress and injury, and eventually, death. What determines the life span of a species? Although aging is a complex process involving multiple genetic and environmental factors, it is apparent that it is a spontaneous process predetermined by the physiological responses to environmental stresses accumulated throughout life. Many of the factors involved in aging localize in the nucleolus, a specialized structure inside every human cell.How do the structure and composition of nucleoli change during aging? How are events that occur in nucleoli affected by aging? Are there factors in the nucleolus that control aging?The principal investigator proposes to isolate nucleoli from human cells at different stages of aging, and map the global flux of all nuclear proteins into and out of the nucleolus during cell senescence by a novel quantitative mass spectrometry technique. The data obtained from this project will lead to the discovery of biological markers for proliferation and/or senescence. Knowledge obtained from the research will contribute to the fields of stem cell biology, cancer, and aging.