title: Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians.
abstract: Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.
authors.affiliation: Department of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. gil.atzmon@einstein.yu.edu
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.forename: Miook
authors.initials: M
authors.lastname: Cho
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: Temuri
authors.initials: T
authors.lastname: Budagov
authors.forename: Micol
authors.initials: M
authors.lastname: Katz
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Yang
authors.forename: Glenn
authors.initials: G
authors.lastname: Siegel
authors.forename: Aviv
authors.initials: A
authors.lastname: Bergman
authors.forename: Derek M
authors.initials: DM
authors.lastname: Huffman
authors.forename: Clyde B
authors.initials: CB
authors.lastname: Schechter
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.forename: Diddahally R
authors.initials: DR
authors.lastname: Govindaraju
authors.forename: Yousin
authors.initials: Y
authors.lastname: Suh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008055:Lipids / Q000097:blood; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D016615:Telomere
chemical_list: D008055:Lipids; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase