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

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 u...

Full description

Saved in:
Bibliographic Details
Published in:PLoS biology Vol. 18; no. 1; p. e3000599
Main Authors: Basisty, Nathan, Kale, Abhijit, Jeon, Ok Hee, Kuehnemann, Chisaka, Payne, Therese, Rao, Chirag, Holtz, Anja, Shah, Samah, Sharma, Vagisha, Ferrucci, Luigi, Campisi, Judith, Schilling, Birgit
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.01.2020
Public Library of Science (PLoS)
Subjects:
Aging
Aging - metabolism
Arthritis
BASIC BIOLOGICAL SCIENCES
Biology and Life Sciences
Biomarkers
Biomarkers - analysis
Biomarkers - metabolism
Blood plasma
Candidates
Cell division
Cells, Cultured
Cellular Senescence - physiology
Correlation analysis
Cytokines
Databases, Protein
Deoxyribonucleic acid
DNA
epithelial cells
exosomes
Exosomes - chemistry
Exosomes - metabolism
Female
Fibroblasts
Gene expression
Genotype & phenotype
Growth factors
HIV
Human immunodeficiency virus
Humans
Laboratories
Longitudinal studies
Mass spectrometry
Medicine and Health Sciences
Methods and Resources
Neurodegeneration
Phenotype
Phenotypes
Protease inhibitors
Proteinase inhibitors
Proteins
Proteome - analysis
Proteome - metabolism
Proteomics
Scientific imaging
Secretory Pathway - physiology
Senescence
Serine
Serine proteinase
Serine proteinase inhibitors
Software
Stanniocalcin
Therapeutic applications
transcriptome analysis
United States > US
California
ISSN:1545-7885, 1544-9173, 1545-7885
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
AC02-05CH11231; AG060906-02; P01AG017242; R01AG051729; 1S10 OD016281; UWPR95794
USDOE Office of Science (SC)
SENS Foundation
National Institutes of Health (NIH)
Glenn Foundation for Medical Research
University of Washington
National Institute on Aging
Current address: Korea University College of Medicine, Seoul, Republic of Korea
I have read the journal’s policy and the authors of this manuscript have the following competing interests: JC is a founder and shareholder of Unity Biotechnology, which develops senolytic drugs. All other authors have declared no competing interests.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.3000599