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myotonic dystrophy - IDMC.org

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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

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