A proteomic atlas of senescence-associated secretomes for aging biomarker development
By N. Basisty, Abhijit Kale, Ok-hee Jeon, Chisaka Kuehnemann, Therese Payne, C. Rao, A. Holtz, Samah Shah, Vagisha Sharma, Luigi Ferrucci and 2 more. bioRxiv, 2019
1,116 citations recorded by the source corpus.
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 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. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including GDF15, STC1 and SERPINs, which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging. 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. Abbreviations ATV, atazanavir treatment; BLSA, Baltimore Longitudinal Study of Aging; CTL, control; DDA, data-dependent acquisition; DAMP, damage-associated molecular pattern; DIA, data-independent acquisition; eSASP, extracellular vesicle senescence associated secretory phenotype; EVs, extracellular vesicles; IR, X-irradiation; MS, mass spectrometry; RAS, inducible RAS overexpression; SA-β-Gal, senescence-associated β-galactosidase; SEN, senescent; sSASP, soluble senescence associated secretory phenotype.
Subfields: Aging, Physiology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/460cd379c418507022e0e3e7f865e83e5023a91a
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Citations in the corpus
- Inflammation and aging: signaling pathways and intervention therapies (2023, background): “Interestingly, some of these components overlap with aging markers observed in human plasma, including serine protease inhibitors, stanniocalcin 1, and growth differentiation factor 15.(190) Furthermore, dysfunctional mitochondria,(195) persistent DNA damage response,(196) CCAAT/enhancer-binding pro”
- Senescence and the SASP: many therapeutic avenues (2020, background): “The true extent of the SASP is now better understood; it is also comprised of hundreds of protein and non-protein signaling molecules, including proteases, hemostatic factors, ceramides, bradykinins, extracellular matrix (ECM) components, and damage-associated molecular patterns (DAMPs) (Davalos et ”
- The senescence-associated secretory phenotype and its physiological and pathological implications (2024, neutral): “…biased proteomics techniques and, less prominently, unbiased proteomics techniques are used to identify upregulation of SASP proteins in the blood 11,22 , whereas mRNA-based methods and immunostaining assays are classically used to check upregulation of SASP expression in different organs 4,11,20 .”