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I.R.F. / Aging news / Diseases / 13052501

Advancing Age and Telomere Uncapping in Arteries
Posted on: May 25, 2013

Arterial telomere dysfunction may contribute to chronic arterial inflammation by inducing cellular senescence and subsequent senescence-associated inflammation. Though telomere shortening has been associated with arterial aging in humans, age-related telomere uncapping has not been described in non-cultured human tissues and may have substantial prognostic value.

In skeletal muscle feed arteries from 104 younger, middle-aged, and older adults, scientists assessed the potential role of age-related telomere uncapping in arterial inflammation.

Telomere uncapping, measured by p-histone γ-H2A.X, ser139 localized to telomeres (chromatin immunoprecipitation; ChIP) and telomeric repeat binding factor 2 bound to telomeres (ChIP) was greater in arteries from older adults compared with those from younger adults. There was greater tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence, measured by P53 bound to P21 gene promoter (ChIP), and greater expression of P21, interleukin 8, and monocyte chemotactic protein 1 mRNA (RT-PCR) in arteries from older adults compared with younger adults. Telomere uncapping was a highly influential covariate for the age-group difference in P53/P21-induced senescence.

Despite progressive age-related telomere shortening in human arteries, mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence.

Collectively, these findings demonstrate that advancing age is associated with greater telomere uncapping in arteries, which is linked to P53/P21-induced senescence independent of telomere shortening.

Keywords: aging, arteries, inflammation, senescence, telomeres.

Source: Morgan RG, Ives SJ, Lesniewski LA, Cawthon RM, Andtbacka RH, Noyes RD, Richardson RS, Donato AJ.; Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries.; Am J Physiol Heart Circ Physiol. 2013 May 10. [Epub ahead of print]
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