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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1710-1717 |
| Number of pages | 8 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | SUPPL. 1 |
| DOIs | |
| State | Published - Jan 26 2010 |
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Keywords
- Aging
- Biomarker
- Heritability
- Longevity
ASJC Scopus subject areas
- General
Cite this
Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. / Atzmon, Gil; Cho, Miook; Cawthon, Richard M.; Budagov, Temuri; Katz, Micol; Yang, Xiaoman; Siegel, Glenn; Bergman, Aviv; Huffman, Derek M.; Schechter, Clyde B.; Wright, Woodring E.; Shay, Jerry W.; Barzilai, Nir; Govindaraju, Diddahally R.; Suh, Yousin.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. SUPPL. 1, 26.01.2010, p. 1710-1717.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians
AU - Atzmon, Gil
AU - Cho, Miook
AU - Cawthon, Richard M.
AU - Budagov, Temuri
AU - Katz, Micol
AU - Yang, Xiaoman
AU - Siegel, Glenn
AU - Bergman, Aviv
AU - Huffman, Derek M.
AU - Schechter, Clyde B.
AU - Wright, Woodring E.
AU - Shay, Jerry W.
AU - Barzilai, Nir
AU - Govindaraju, Diddahally R.
AU - Suh, Yousin
PY - 2010/1/26
Y1 - 2010/1/26
N2 - 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.
AB - 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.
KW - Aging
KW - Biomarker
KW - Heritability
KW - Longevity
UR - http://www.scopus.com/inward/record.url?scp=76549104441&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76549104441&partnerID=8YFLogxK
U2 - 10.1073/pnas.0906191106
DO - 10.1073/pnas.0906191106
M3 - Article
VL - 107
SP - 1710
EP - 1717
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - SUPPL. 1
ER -