The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Senescence-associated β-galactosidase is lysosomal β-galactosidase.
Open accessAbstract
Summary: Replicative senescence limits the proliferation of somatic cells passaged in culture and may reflect cellular aging in vivo . The most widely used biomarker for senescent and aging cells is senescence‐associated β‐galactosidase (SA‐β‐gal), which is defined as β‐galactosidase activity detectable at pH 6.0 in senescent cells, but the origin of SA‐β‐gal and its cellular roles in senescence are not known. We demonstrate here that SA‐β‐gal activity is expressed from GLB1 , the gene encoding lysosomal β‐D‐galactosidase, the activity of which is typically measured at acidic pH 4.5. Fibroblasts from patients with autosomal recessive G M1 ‐gangliosidosis, which have defective lysosomal β‐galactosidase, did not express SA‐β‐gal at late passages even though they underwent replicative senescence. In addition, late passage normal fibroblasts expressing small‐hairpin interfering RNA that depleted GLB1 mRNA underwent senescence but failed to express SA‐β‐gal. GLB1 mRNA depletion also prevented expression of SA‐β‐gal activity in HeLa cervical carcinoma cells induced to enter a senescent state by repression of their endogenous human papillomavirus E7 oncogene. SA‐β‐gal induction during senescence was due at least in part to increased expression of the lysosomal β‐galactosidase protein. These results also indicate that SA‐β‐gal is not required for senescence.
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“Experimentally, SA-β-gal staining20 and expression of cyclin-dependent kinase (CDK) inhibitors like p16 and p21 are commonly used to characterize senescence.”
From Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators (2024) · cites this paper as [20]
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In the citing paper
“The outer layer of the animal body is readily accessible for sample collection and is suitable as an index organ for aging and age-related pathologies of internal organs, such as the cardiovascular system, bones, and brain51–53, among others.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [51]
Experimental — accuracy not yet measuredIn the citing paper
“One characteristic feature of senescent cells is increased lysosomal activity (Kurz et al., 2000; Lee et al., 2006), macromolecular damage (Gorgoulis et al., 2019), and a temporal cascade in the development of the complex senescence-associated secretory phenotype (SASP) (Coppé et al., 2008, 2010a; Saleh et al., 2018).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Lee et al., 2006
In the citing paper
“Cellular senescence is associated with changes in cellular metabolism. These include upregulation of lysosomal senescence-associated β-galactosidase, a shift from oxidative phosphorylation to glycolysis [54,55] and accumulation of lipofuscin in the cytoplasm [56,57].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [54]
In the citing paper
“As β-gal is not required for senescence40”
From Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence (2024) · cites this paper as [40]
In the citing paper
“Studies of cells with defective lysosomal β-galactosidase have shown that β–galactosidase does not trigger cellular senescence [71, 72] and only accompanies senescent alterations.”
From Markers of cellular senescence. Telomere shortening as a marker of cellular senescence (2016) · cites this paper as [71]
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Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,379
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220
Kurz, D. J., Decary, S., Hong, Y., & Erusalimsky, J. D. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.20.3613 · Cited by 899
Senescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826
Oxidative DNA damage and senescence of human diploid fibroblast cells.
Chen, Q., Fischer, A., Reagan, J. D., Yan, L. J., & Ames, B. N. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4337 · Cited by 720
Cited by
Sorted by citations
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070
“(c) Senescent cells express a senescence-associated -galactosidase (SA-Bgal; Dimri et al., 1995), which partly reflects the increase in lysosomal mass (Lee et al., 2006).”
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622
Metadata
- Authors
- Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S.
- Affiliations
- University of Seoul (KR)
- University of Florence (IT)
- Yale University (US)
- Erasmus MC (NL)
- Corresponding author
- DiMaio, Daniel
- Hwang, Eun Seong
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2006-03-17
- Volume
- 5
- Issue
- 2
- Pages
- 187-195
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W1995205742
- Cited by
- 1,444
- References
- 49
- Citations by year
- 2026: 95 · 2025: 138 · 2024: 177 · 2023: 157 · 2022: 131 · 2021: 119 · 2020: 108 · 2019: 63 · 2018: 69 · 2017: 58 · 2016: 57 · 2015: 46 · 2014: 44 · 2013: 28 · 2012: 32
- FWCI
- 14.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Yale University
- Korea Science and Engineering Foundation
- National Cancer Institute (CA-16038, P01CA016038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- senescence-associated β-galactosidase, lysosomal beta-galactosidase, GLB1, replicative senescence, cellular aging, fibroblasts, human papillomavirus E7, siRNA knockdown, senescence biomarkers, lysosomal enzyme activity
- MeSH terms
- beta-Galactosidase, Cells, Cultured, Fibroblasts, Gangliosidoses, HeLa Cells, Humans, Lysosomes, Mutation, Cellular Senescence, RNA Interference
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