title: Short telomeres are sufficient to cause the degenerative defects associated with aging.
abstract: Telomerase function is critical for telomere maintenance. Mutations in telomerase components lead to telomere shortening and progressive bone marrow failure in the premature aging syndrome dyskeratosis congenita. Short telomeres are also acquired with aging, yet the role that they play in mediating age-related disease is not fully known. We generated wild-type mice that have short telomeres. In these mice, we identified hematopoietic and immune defects that resembled those present in dyskeratosis congenita patients. When mice with short telomeres were interbred, telomere length was only incrementally restored, and even several generations later, wild-type mice with short telomeres still displayed degenerative defects. Our findings implicate telomere length as a unique heritable trait that, when short, is sufficient to mediate the degenerative defects of aging, even when telomerase is wild-type.
authors: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. marmani1@jhmi.edu
authors: Mary
authors: M
authors: Armanios
authors: Jonathan K
authors: JK
authors: Alder
authors: Erin M
authors: EM
authors: Parry
authors: Baktiar
authors: B
authors: Karim
authors: Margaret A
authors: MA
authors: Strong
authors: Carol W
authors: CW
authors: Greider
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D019871:Dyskeratosis Congenita / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D007075:Immunoglobulin M; D019098:Telomerase