{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T05:24:26Z","timestamp":1794201866827,"version":"4.8.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T00:00:00Z","timestamp":1142553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Replicative senescence limits the proliferation of somatic cells passaged in culture and may reflect cellular aging\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The most widely used biomarker for senescent and aging cells is senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal), which is defined as \u03b2\u2010galactosidase activity detectable at pH 6.0 in senescent cells, but the origin of SA\u2010\u03b2\u2010gal and its cellular roles in senescence are not known. We demonstrate here that SA\u2010\u03b2\u2010gal activity is expressed from\n                    <jats:italic>GLB1<\/jats:italic>\n                    , the gene encoding lysosomal \u03b2\u2010D\u2010galactosidase, the activity of which is typically measured at acidic pH 4.5. Fibroblasts from patients with autosomal recessive G\n                    <jats:sub>M1<\/jats:sub>\n                    \u2010gangliosidosis, which have defective lysosomal \u03b2\u2010galactosidase, did not express SA\u2010\u03b2\u2010gal at late passages even though they underwent replicative senescence. In addition, late passage normal fibroblasts expressing small\u2010hairpin interfering RNA that depleted\n                    <jats:italic>GLB1<\/jats:italic>\n                    mRNA underwent senescence but failed to express SA\u2010\u03b2\u2010gal.\n                    <jats:italic>GLB1<\/jats:italic>\n                    mRNA depletion also prevented expression of SA\u2010\u03b2\u2010gal activity in HeLa cervical carcinoma cells induced to enter a senescent state by repression of their endogenous human papillomavirus E7 oncogene. SA\u2010\u03b2\u2010gal induction during senescence was due at least in part to increased expression of the lysosomal \u03b2\u2010galactosidase protein. These results also indicate that SA\u2010\u03b2\u2010gal is not required for senescence.\n                  <\/jats:p>","DOI":"10.1111\/j.1474-9726.2006.00199.x","type":"journal-article","created":{"date-parts":[[2006,3,17]],"date-time":"2006-03-17T06:21:26Z","timestamp":1142576486000},"page":"187-195","source":"Crossref","is-referenced-by-count":1390,"title":["Senescence\u2010associated \u03b2\u2010galactosidase is lysosomal \u03b2\u2010galactosidase"],"prefix":"10.1111","volume":"5","author":[{"given":"Bo Yun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung A.","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Sub","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Morrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Johung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Goodwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim J.","family":"Kleijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"DiMaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Seong","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/261499a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03841"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00083-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(73)90484-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20147"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4337"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1073"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/436642a"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2005.08.005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(75)90004-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(68)90071-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.1551-1563.2003"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9363"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000109185"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0047-6374(90)90005-Z"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2005.06.003"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(03)00132-3"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.20.10978"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(61)90192-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(02)00102-1"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1128\/jvi.67.7.3720-3729.1993","article-title":"Inhibition of cervical carcinoma cell line proliferation by introduction of a bovine papillomavirus regulatory gene","volume":"67","author":"Hwang ES","year":"1993","journal-title":"J. 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