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Abstract No : 18<br />
ORAL PRESENTATIONS<br />
TELOMERE SHORTENING AND REPLICATIVE SENESCENCE<br />
IN DM1 IN VITRO AND IN VIVO<br />
Xu W., Sarkar P. S., Gao R. and Ashizawa T.<br />
Department of Neurology, UTMB, Galveston, TX, 77550-00874, USA<br />
Patients with DM1 often develop clinical signs resembling accelerated aging, such as<br />
muscle weakness and wasting, insulin resistance, dilated cardiomyopathy with cardiac<br />
conduction abnormalities, chronic constipation, cataract, testicular atrophy, balding,<br />
and hearing loss. We previously showed that DM1 lymphoblastoid cell lines (LBCLs)<br />
exhibit accelerated cell-cycling and shortened lifespan in culture. To explore the relationship<br />
between the high rate of proliferation and the accelerated cellular aging, we<br />
examined the telomere length and replicative potentials of DM1 cells. DM1 LBCLs exhibited<br />
faster telomere shortening with decreased lifespan and senescence-associated morphological<br />
changes. The rate of telomere shortening correlated with the CTG repeat<br />
expansion size. DM1 fibroblasts showed a similar number of population doublings and<br />
viability as their age/sex matched controls before reaching the replicative senescence.<br />
However, DM1 fibroblasts showed significantly higher BrdU incorporation and a faster<br />
proliferation rate than the normal controls (p