Protocols to detect senescence-associated beta-galactosidase (SA-βgal) activity, a biomarker of senescent cells in culture and in vivo
Open accessAbstract
Normal cells can permanently lose the ability to proliferate when challenged by potentially oncogenic stress, a process termed cellular senescence. Senescence-associated beta-galactosidase (SA-betagal) activity, detectable at pH 6.0, permits the identification of senescent cells in culture and mammalian tissues. Here we describe first a cytochemical protocol suitable for the histochemical detection of individual senescent cells both in culture and tissue biopsies. The second method is based on the alkalinization of lysosomes, followed by the use of 5-dodecanoylaminofluorescein di-beta-D-galactopyranoside (C12FDG), a fluorogenic substrate for betagal activity. The cytochemical method takes about 30 min to execute, and several hours to a day to develop and score. The fluorescence methods take between 4 and 8 h to execute and can be scored in a single day. The cytochemical method is applicable to tissue sections and requires simple reagents and equipment. The fluorescence-based methods have the advantages of being more quantitative and sensitive.
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The FACS method based on SPiDER-β-gal labels all SA-β-gal+ cells.
“we established a fluorescence-activated cell sorting (FACS) method based on the fluorescent probe SPiDER-β-gal (hereafter, SPiDER; similar to the C12FDG fluorescent probe)25,26, which labels all SA-β-gal+ cells (Extended Data Fig. 1d).”
From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [26]
During aging, the cytotoxic activity of immune cells decreases, and the expression of functional molecules associated with cytotoxic activity, such as IFN-γ, granzyme B, and perforin, is reduced.
“More recent studies have shown that, during aging, the cytotoxic activity of immune cells decreases, and the expression of functional molecules associated with cytotoxic activity, such as interferon gamma (IFN-γ), granzyme B, and perforin, is also reduced [31–34] (Table 1).”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [34]
SA-βgal is a known marker of senescent cells.
“senescence-associated beta-galactosidase (SA-βgal), a known marker of senescent cells (Debacq-Chainiaux et al., 2009)”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Debacq-Chainiaux et al., 2009
Increased activity of lysosomal β-galactosidase is a primary characteristic of senescent cells, exploited as SA-β-gal.
“To specifically target senescent cells, we focused on one primary characteristic of senescent cells — the increased activity of lysosomal β-galactosidase, exploited as senescence-associated β-galactosidase (SA-β-gal).18,19”
From Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice (2020) · cites this paper as [19]
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- Authors
- Debacq-Chainiaux, F., Erusalimsky, J. D., Campisi, J., & Toussaint, O.
- Affiliations
- Cardiff Metropolitan University (GB)
- Buck Institute for Research on Aging (US)
- University of Namur (BE)
- Corresponding author
- Toussaint, Olivier
- Venue
- Nature Protocols
- Published
- 2009-11-19
- Volume
- 4
- Issue
- 12
- Pages
- 1798-1806
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- OpenAlex
- W2010345740
- Cited by
- 1,668
- References
- 9
- Citations by year
- 2026: 123 · 2025: 147 · 2024: 160 · 2023: 135 · 2022: 132 · 2021: 150 · 2020: 131 · 2019: 112 · 2018: 117 · 2017: 90 · 2016: 99 · 2015: 79 · 2014: 60 · 2013: 63 · 2012: 34
- FWCI
- 15.46
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Protocols (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Repository of the University of Namur (submittedVersion)
- Cardiff Metropolitan Research Repository (Cardiff Metropolitan University) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- British Heart Foundation
- National Institute on Aging (AG017242, AG-09909, P30AG025708, AG032117, AG025708, P01AG017242)
- National Cancer Institute (CA0126540)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- senescence-associated β-galactosidase, cellular senescence, senescent cells, cytochemical detection, histochemical staining, lysosomal alkalinization, fluorogenic substrates, tissue sections, tissue biopsy, senescence biomarkers
- MeSH terms
- beta-Galactosidase, Fluoresceins, Galactosides, Histocytochemistry, Hydrogen-Ion Concentration, Lysosomes, Microscopy, Fluorescence, Biomarkers, Cellular Senescence
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