title: Age-related arterial telomere uncapping and senescence is greater in women compared with men.
abstract: Telomere uncapping increases with advancing age in human arteries and this telomere uncapping is associated with increased markers of senescence, independent of mean telomere length. However, whether there are sex specific differences in arterial telomere uncapping is unknown. We found that telomere uncapping (serine 139 phosphorylated histone γ-H2A.X in telomeres) in arteries was ~2.5 fold greater in post-menopausal women (n=17, 63±2 years) compared with pre-menopausal women (n=11, 30±2 years, p=0.02), while there was only a trend towards greater telomere uncapping in older men (n=26, 66±2 years) compared with young men (n=11, 31±2, p=0.11). Senescence markers, p53 bound to the p21 gene promoter and p21 gene expression, were 3-4 fold greater in post-menopausal compared with pre-menopausal women (p=0.01-0.02), but only 1.5-2 fold greater in older compared with young men (p=0.02-0.08). Blood glucose was related to telomere uncapping in women, while systolic blood pressure, pulse pressure and serum creatinine were related to telomere uncapping in men. Mean arterial telomere length decreased similarly in women and men with age (p<0.01). Thus, the age-related increase in arterial telomere uncapping and senescence is greater in women than men, despite similar age-related reductions in mean telomere length in both sexes.
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Research Department, Navy Experimental Diving Unit, Panama City, FL, USA.
authors.forename: R Garrett
authors.initials: RG
authors.lastname: Morgan
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT, USA; Health and Exercise Sciences Department, Skidmore College, Saratoga Springs, NY, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Robert H I
authors.initials: RH
authors.lastname: Andtbacka
authors.affiliation: Department of Surgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Noyes
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA; Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, Veteran's Affairs Medical Center, Salt Lake City, UT, USA. Electronic address: tony.donato@utah.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology; D001158:Arteries / Q000503:physiopathology / Q000648:ultrastructure*; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017698:Postmenopause / Q000235:genetics / Q000502:physiology; D017697:Premenopause / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000502:physiology*; D059506:Telomere Shortening / Q000502:physiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C468783:H2AX protein, human; D006657:Histones; D019098:Telomerase
keywords: Aging; Artery; Senescence; Sex differences; Telomere dysfunction