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

Nathan Basisty 1 , Abhijit Kale 1 , Ok Hee Jeon 1 , Chisaka Kuehnemann 1 , Therese Payne 1 , Chirag Rao 1 , Anja Holtz 1 , Samah Shah 1 , Vagisha Sharma 2 , Luigi Ferrucci 3 , Judith Campisi 1, 4 , Birgit Schilling ** 1

1 The Buck Institute for Research on Aging, Novato, California 94947, USA.
2 University of Washington, Seattle, Washington 98105, USA
3 Intramural Research Program of the National Institute on Aging, NIH, Baltimore, Maryland, 21225, USA.
4 Lawence Berkeley Laboratory, University of California, Berkeley, California 94720,USA.
** Correspondence: bschilling@buckinstitute.org

SUMMARY: The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the “SASP Atlas,” a comprehensive proteomic database of soluble proteins and exosomal cargo 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. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin 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)
    Created and managed at the Buck Institute for Research on Aging