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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SA-β-gal staining and expression of CDK inhibitors like p16 and p21 are commonly used to characterize senescence.
“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]
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.
“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]
The Introduction discusses senescence markers in aging tissues, and Experimental procedures describes fibroblasts obtained from skin biopsies. Neither section says skin is readily accessible for sampling or can serve as an index of aging and disease in internal organs. Searches for those concepts returned no supporting passage; page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSenescent cells have increased lysosomal activity.
“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
Cellular senescence is associated with changes in cellular metabolism including upregulation of lysosomal senescence-associated β-galactosidase, a shift from oxidative phosphorylation to glycolysis, and accumulation of lipofuscin in the cytoplasm.
“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]
Beta-galactosidase is not required for senescence.
“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]
Studies of cells with defective lysosomal β-galactosidase have shown that β-galactosidase does not trigger cellular senescence and only accompanies senescent alterations.
“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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- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology › 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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