Senescence-associated beta-galactosidase explained

Senescence-associated beta-galactosidase (SA-β-gal or SABG) is a hypothetical hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. Senescence-associated beta-galactosidase, along with p16^Ink4A, is regarded to be a biomarker of cellular senescence.^{[1] [2]}

Its existence was proposed in 1995 by Dimri et al.^[3] following the observation that when beta-galactosidase assays were carried out at pH 6.0, only cells in senescence state develop staining. They proposed a cytochemical assay based on production of a blue-dyed precipitate that results from the cleavage of the chromogenic substrate X-Gal, which stains blue when cleaved by galactosidase. Since then, even more specific quantitative assays were developed for its detection at pH 6.0.^{[4] [5] [6]}

Today this phenomenon is explained by the overexpression and accumulation of the endogenous lysosomal beta-galactosidase specifically in senescent cells.^[7] Its expression is not required for senescence.^[8] However, it remains as the most widely used biomarker for senescent and aging cells, because it is easy to detect and reliable both in situ and in vitro.

Further reading

• Yang NC, Hu ML . October 2005 . The limitations and validities of senescence associated-beta-galactosidase activity as an aging marker for human foreskin fibroblast Hs68 cells . Exp. Gerontol. . 40 . 10 . 813–9 . 10.1016/j.exger.2005.07.011 . 16154306 . 30500511.

Notes and References

1. Hall BM, Balan V, Gleiberman AS, Strom E, Krasnov P, Virtuoso LP, Rydkina E, Vujcic S, Balan K, Gitlin I, Leonova K, Polinsky A, Chernova OB, Gudkov AV . 2016 . Aging of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells . . 8 . 7 . 1294–1315 . 10.18632/aging.100991 . 4993332 . 27391570.
2. Hall BM, Balan V, Gleiberman AS, Strom E, Krasnov P, Virtuoso LP, Rydkina E, Vujcic S, Balan K, Gitlin II, Leonovo KI, Consiglio CR, Gollnick SO, et al. . 2017 . p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli . Aging . Albany NY . 9 . 8 . 1867–1884 . 10.18632/aging.101268 . 5611982 . 28768895.
3. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O . September 1995 . A biomarker that identifies senescent human cells in culture and in aging skin in vivo . Proc. Natl. Acad. Sci. U.S.A. . 92 . 20 . 9363–7 . 1995PNAS...92.9363D . 10.1073/pnas.92.20.9363 . 40985 . 7568133 . free.
4. Bassaneze V, Miyakawa AA, Krieger JE . January 2008 . A quantitative chemiluminescent method for studying replicative and stress-induced premature senescence in cell cultures . Anal. Biochem. . 372 . 2 . 198–203 . 10.1016/j.ab.2007.08.016 . 17920029.
5. Gary RK, Kindell SM . August 2005 . Quantitative assay of senescence-associated beta-galactosidase activity in mammalian cell extracts . Anal. Biochem. . 343 . 2 . 329–34 . 10.1016/j.ab.2005.06.003 . 16004951.
6. Book: Biological Aging . Itahana K, Campisi J, Dimri GP . Humana Press . 2007 . 978-1-58829-658-0 . Methods in Molecular Biology . 371 . 21–31 . Methods to Detect Biomarkers of Cellular Senescence . 10.1007/978-1-59745-361-5_3 . 17634571 . https://archive.org/details/biologicalagingm00toll/page/21 . registration.
7. Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC, Kleijer WJ, DiMaio D, Hwang ES . April 2006 . Senescence-associated beta-galactosidase is lysosomal beta-galactosidase . Aging Cell . 5 . 2 . 187–95 . 10.1111/j.1474-9726.2006.00199.x . 16626397 . 82432911 . free . 2158/216175.
8. Lee BY, Han JA, Im JS, Morrone A, Johung K, Goodwin EC, Kleijer WJ, DiMaio D, Hwang ES . April 2006 . Senescence-associated beta-galactosidase is lysosomal beta-galactosidase . Aging Cell . 5 . 2 . 187–95 . 10.1111/j.1474-9726.2006.00199.x . 16626397 . 82432911 . free . 2158/216175.