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

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.

Authors:

Basisty, Nathan  ^[1];

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Kale, Abhijit  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-1105-6953"
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Jeon, Ok Hee  ^[2];

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Kuehnemann, Chisaka ^[1]; Payne, Therese ^[1]; Rao, Chirag  ^[1];

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• Search DOE PAGES for ORCID "0000-0002-6106-1144"
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Holtz, Anja  ^[1];

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Shah, Samah ^[1]; Sharma, Vagisha  ^[3];

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Ferrucci, Luigi ^[4]; Campisi, Judith ^[5]; Schilling, Birgit ^[1]; Serrano, Manuel ^[6]

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+ Show Author Affiliations

1. The Buck Inst. for Research on Aging, Novato, CA (United States)
2. The Buck Inst. for Research on Aging, Novato, CA (United States); Korea Univ. College of Medicine, Seoul (Korea)
3. Univ. of Washington, Seattle, WA (United States)
4. National Inst. of Health (NIH), Baltimore, MD (United States)
5. The Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
6. International Review Board (IRB), Barcelona (Spain)

Publication Date:

2020-01-16

Research Org.:

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC); National Institute on Aging; National Institutes of Health (NIH); Glenn Foundation for Medical Research; SENS Foundation; University of Washington

OSTI Identifier:

1603602

Grant/Contract Number:  

[AC02-05CH11231; AG060906-02; P01AG017242; R01AG051729; 1S10 OD016281; UWPR95794]

Resource Type:

Accepted Manuscript

Journal Name:

PLoS biology (Online)

Additional Journal Information:

[Journal Name: PLoS biology (Online); Journal Volume: 18; Journal Issue: 1]; Journal ID: ISSN 1545-7885

Publisher:

Public Library of Science

Country of Publication:

United States

Language:

English

Subject:

fibroblasts; biomarkers; epithelial cells; senescence; transcriptome analysis; exosomes; blood plasma