A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development

Authors: Nathan Basisty 1 , Abhijit Kale 1 , Okhee Jeon 1 , Chisaka Kuehnemann 1 , Therese Payne 1 , Chirag Rao 1 , Anja Holtz 1 , Samah Shah 1 , Luigi Ferrucci 3 , Judith Campisi 1, 2 , Birgit Schilling ** 1
1 The Buck Institute for Research on Aging, Novato, California 94947, USA.
2 Lawence Berkeley Laboratory, University of California, Berkeley, California 94720,USA.
3 National Institute on Aging, Bethesda, Maryland 20892, USA.
** Correspondence: bschilling@buckinstitute.org

SUMMARY: The senescence-associated secretory phenotype (SASP) has recently emerged as both a driver of, and promising therapeutic target for, multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically monitored by a few dozen secreted proteins, has been greatly underappreciated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present ‘SASP Atlas’, a comprehensive proteomic database of soluble and exosome SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins, but also includes a subset of proteins elevated in all SASPs. Based on our analyses, we propose several candidate biomarkers of cellular senescence, including GDF15, STC1 and SERPINs. This resource will facilitate identification of proteins that drive specific senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus and tissue of senescent cells in vivo.

Senescence Inducers

The senescence-associated secretory phenotype (SASP) of human fibroblasts following induction of senescence by various stimuli.

  • X-ray irradiation (genotoxic stress-induced)
  • RAS overexpression (oncogene-induced)
  • Atazanivir treatment (treatment-induced)
  • Cell Types

    The senescence-associated secretory phenotype (SASP) of different human primary cell types.

  • Fibroblasts
  • Epithelial Cells
  • Exosomes

    The exosome SASP of primary human cells following induction of senescence by various stimuli.

  • X-ray irradiation
  • RAS overexpression
  • SASP Query Tool

    Are your proteins in the SASP? Enter a list of gene names to display secretion levels in various SASPs.
    **Generously provided by Kevin Perez (Buck Institute)