title: Senescence-associated beta-galactosidase is lysosomal beta-galactosidase.
abstract: 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 beta-galactosidase (SA-beta-gal), which is defined as beta-galactosidase activity detectable at pH 6.0 in senescent cells, but the origin of SA-beta-gal and its cellular roles in senescence are not known. We demonstrate here that SA-beta-gal activity is expressed from GLB1, the gene encoding lysosomal beta-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 beta-galactosidase, did not express SA-beta-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-beta-gal. GLB1 mRNA depletion also prevented expression of SA-beta-gal activity in HeLa cervical carcinoma cells induced to enter a senescent state by repression of their endogenous human papillomavirus E7 oncogene. SA-beta-gal induction during senescence was due at least in part to increased expression of the lysosomal beta-galactosidase protein. These results also indicate that SA-beta-gal is not required for senescence.
authors.affiliation: Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong, Seoul, Korea 130-743.
authors.forename: Bo Yun
authors.initials: BY
authors.lastname: Lee
authors.forename: Jung A
authors.initials: JA
authors.lastname: Han
authors.forename: Jun Sub
authors.initials: JS
authors.lastname: Im
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Kimberly
authors.initials: K
authors.lastname: Johung
authors.forename: Edward C
authors.initials: EC
authors.lastname: Goodwin
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology; D005733:Gangliosidoses / Q000201:enzymology; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D034622:RNA Interference; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: C061901:GLB1 protein, human; D001616:beta-Galactosidase