{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:24:00Z","timestamp":1772227440145,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,10,2]],"date-time":"2003-10-02T00:00:00Z","timestamp":1065052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Normal somatic cells have a finite replicative capacity. With each cell division, telomeres shorten progressively until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell types in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. In this study, we show that telomere shortening accompanied by low to moderate telomerase activity, and ultimately senescence, occurs in rat microglia in vitro. When microglia are stimulated to divide with the mitogen granulocyte macrophage\u2010colony stimulating factor (GM\u2010CSF), longer telomeres are allowed to shorten, while shorter telomeres are lengthened. Telomerase activity is nearly 3\u2010fold higher in GM\u2010CSF\u2010stimulated microglia initially, relative to unstimulated controls, and then declines to levels below those seen in controls before increasing again. Telomere attrition is also more rapid when microglia are grown in culture dishes of increasing size. Fluorescence in situ hybridization (FISH) analysis indicates that a nearly 3\u2010fold variation in both inter\u2010 and intra\u2010chromosomal telomere length exists in microglia. In contrast to microglia, cultured astrocytes exhibit a cyclical pattern of telomere lengthening and shortening over time, corresponding to a similar cycle of higher and lower telomerase activity. When astrocytes are passaged, mean telomere length increases initially from passage 1\u20132, remaining constant until passage 5, while the shortest telomeres are continually lengthened. In conclusion, the telomere shortening evident in microglia is accompanied by their progression to senescence by 32 days in vitro. In contrast, astrocytes, perhaps due to greater telomerase activity, have longer life spans and may be passaged repeatedly before entering senescence. Our findings provide an impetus to investigate the possibility that microglial telomere shortening may occur in vivo. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10301","type":"journal-article","created":{"date-parts":[[2003,12,2]],"date-time":"2003-12-02T14:20:52Z","timestamp":1070374852000},"page":"75-88","source":"Crossref","is-referenced-by-count":135,"title":["Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes"],"prefix":"10.1002","volume":"45","author":[{"given":"Barry E.","family":"Flanary","sequence":"first","affiliation":[]},{"given":"Wolfgang J.","family":"Streit","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2003,10,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1995.1213"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10114"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062329"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.10105"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13677"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.349"},{"key":"e_1_2_6_8_1","first-page":"1202","article-title":"Telomerase is a true reverse transcriptase. 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