Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Proteomic Tools to Decipher Mechanisms of Senescence in Aging and Age-related Diseases (#6)

Natan Basisty 1 , Abhijit Kale 1 , Okhee Jeon 1 , Christopher Wiley 1 , Su Liu 1 , Chisaka Kuehnemann 1 , Anja Holtz 1 , Pankaj Kapahi 1 , Luigi Ferrucci 2 , Judith Campisi 1 , Birgit Schilling 1
  1. Buck Institute for Research on Aging, Novato, CA, USA
  2. National Institute on Aging, Bethesda, Maryland , USA

Cellular senescence is a striking example of a prime driver of aging phenotypes and pathologies across multiple tissues. This complex stress response causes an essentially irreversible arrest of cell proliferation and the development of a multi-component senescence-associated secretory phenotype (SASP). We hypothesize that, via the SASP, senescent cells exert cell non-autonomous effects that can disrupt cells and tissues locally and at a distance and contribute to neurodegeneration, thrombosis, and multiple age-related pathologies. Using quantitative SILAC workflows as well as more comprehensive data-independent acquisitions approaches, we have assessed the composition and functions of the SASP in aging and disease contexts. Recently, our proteomic screens have identified a novel role for senescent cells and SASP in hemostasis and blood coagulation. Since senescent cells accumulate with age, we speculate that the SASP is at least partly responsible for thrombotic events that increase with age. The general role of senescent cells as driver of age-related diseases has moved forward potential therapeutics (senolytics) to remove senescent cells to improve health span. Overall, it will be of key importance to identify senescence markers, both as biomarkers for aging and age-related diseases, in order to monitor any therapeutic interventions to eliminate senescent cells. 

This work was supported by the National Institute on Aging (U01 AG060906-01, PI: Schilling; and P01AG017242 and R01AG051729, PI: Campisi) and postdoctoral fellowships by the Glenn Foundation (to NB and OJ).