A proteomic atlas of senescence-associated secretomes for aging biomarker development

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

Research output: Contribution to journalArticlepeer-review

171 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)e3000599
JournalPLoS biology
Volume18
Issue number1
DOIs
Publication statusPublished - 2020 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint

Dive into the research topics of 'A proteomic atlas of senescence-associated secretomes for aging biomarker development'. Together they form a unique fingerprint.

Cite this