Is β-Galactosidase Staining a Marker of Senescence in Vitro and in Vivo?
Abstract
Cytochemically detectable beta-galactosidase (beta-gal) at pH 6.0 has been reported to increase during the replicative senescence of fibroblast cultures and has been used widely as a marker of cellular senescence in vivo and in vitro. In this study, we have characterized changes in senescence-associated (SA) beta-gal staining in early and late passage cultures, cultures established from donors of different ages, virally immortalized cells, and tissue slices obtained from donors of different ages. The effects of different culture conditions were also examined. While we confirm the previous report that SA beta-gal staining increased in low-density cultures of proliferatively senescent cells, we were unable to demonstrate that it is a specific marker for aging in vitro. Cultures established from donors of different ages stained for SA beta-gal activity as a function of in vitro replicative age, not donor age. We also failed to observe any differences in SA beta-gal staining in skin cells in situ as a marker of aging in vivo. The level of cytochemically detectable SA beta-gal was elevated in confluent nontransformed fibroblast cultures, in immortal fibroblast cultures that had reached a high cell density, and in low-density, young, normal cultures oxidatively challenged by treatment with H2O2. Although we clearly demonstrate that SA beta-gal staining in cells is increased under a variety of different conditions, the interpretation of increased staining remains unclear, as does the question of whether the same mechanisms are responsible for the increased SA beta-gal staining observed in senescent cells and changes observed in cells under other conditions.
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SA-β-Gal at pH 6 can be detected in vitro in confluent and immortalized cells and in activated macrophages.
“For example, the commonly used marker senescence-associated β-galactosidase (SA-β-Gal) at pH 6 can be detected in vitro in confluent and immortalized cells6 and in activated macrophages7, while cell cycle kinase inhibitors p16INK4a and p21CIP1 can be expressed irrespectively of senescence in certain contexts7,8.”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [6]
None of the markers used to detect senescent cells are individually specific.
“None of the markers used to detect senescent cells are individually specific.”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [6]
There is no single, stand-alone marker to identify a senescent cell.
“One major challenge is that there is no single, stand-alone marker to identify a senescent cell.”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [6]
SA-β Gal activity is one of the first and most used biomarkers of senescence, although it can be detected in non-senescent cells that are confluent or serum-starved.
“Senescence-associated β-galactosidase (SA-β Gal) activity is one of the first and most used biomarkers of senescence, although it has limitations because it can be detected in non-senescent cells that are confluent or serum-starved [233].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [233]
The β‐gal assay was performed in subconfluent cultures displaying comparable cell density to avoid staining due to cell confluence rather than proliferative senescence.
“To avoid staining due to cell confluence rather than to proliferative senescence (Severino et al., 2000), the assay was performed in subconfluent cultures displaying comparable cell density.”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Severino et al., 2000
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- Authors
- Severino, J., Allen, R. G., Balin, S., Balin, A., & Cristofalo, V. J.
- Affiliations
- Thomas Jefferson University (US)
- Corresponding author
- Cristofalo, Vincent J.
- ORCID
- Balin, Samuel
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 257
- Issue
- 1
- Pages
- 162-171
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2018686812
- Cited by
- 370
- References
- 47
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 21 · 2023: 15 · 2022: 14 · 2021: 17 · 2020: 14 · 2019: 10 · 2018: 12 · 2017: 17 · 2016: 9 · 2015: 19 · 2014: 21 · 2013: 20 · 2012: 15
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7p30ag013282-05)
- National Institute on Aging (AG00378, AG13282)
- 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, replicative senescence, fibroblasts, aging markers, donor age, hydrogen peroxide, oxidative stress, skin cells, culture density, cytochemistry
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, beta-Galactosidase, Cells, Cultured, Child, Female, Humans, Male, Middle Aged, Biomarkers, Cellular Senescence
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