Leukocytes of exceptionally old persons display ultra-short telomeres

被引:44
作者
Kimura, M.
Barbieri, M.
Gardner, J. P.
Skurnick, J.
Cao, X.
van Riel, N.
Rizzo, M. R.
Paoliso, G.
Aviv, A.
机构
[1] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Human Dev & Aging, MSB, Newark, NJ 07103 USA
[2] Univ Naples 2, Dept Geriatr Med & Metab Dis, Naples, Italy
[3] Eindhoven Univ Technol, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands
关键词
aging; centenarians; mortality; replication; lifespan; senescence;
D O I
10.1152/ajpregu.00615.2007
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
With a view to understanding the association between leukocyte telomere length and the human lifespan, we performed genome-wide telomere length analyses by the terminal restriction fragment length (TRFL) and single molecule telomere length analysis (STELA) of the X and Y chromosomes in leukocytes of exceptionally old (aged 90-104 yr) and younger (aged 23-74 yr) individuals. We found that the mean TRFL of 82 exceptionally old individuals was within a range projected by age-dependent TRFL attrition of 99 younger individuals. However, compared with the younger individuals, exceptionally old persons exhibited peaking of the TRFL distribution with overrepresentation of ultra-short telomeres. These findings were confirmed by the STELA. Women had longer mean TRFL than men (6.10 vs. 5.86 kb), and exceptionally old women exhibited fewer ultra-short telomeres than exceptionally old men. Our results have implications for gerontological studies of the limitation of lifespan in humans.
引用
收藏
页码:R2210 / R2217
页数:8
相关论文
共 47 条
[1]  
Alberti KGMM, 1998, DIABETIC MED, V15, P539, DOI 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO
[2]  
2-S
[3]   Healthy centenarians do not exist, but autonomous centenarians do: A population-based study of morbidity among Danish centenarians [J].
Andersen-Ranberg, K ;
Schroll, M ;
Jeune, B .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2001, 49 (07) :900-908
[4]   Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs [J].
Andrew, T ;
Aviv, A ;
Falchi, M ;
Surdulescu, GL ;
Gardner, JP ;
Lu, XB ;
Kimura, M ;
Kato, BS ;
Valdes, AM ;
Spector, TD .
AMERICAN JOURNAL OF HUMAN GENETICS, 2006, 78 (03) :480-486
[5]   Clinical phenotype of families with longevity [J].
Atzmon, G ;
Schechter, C ;
Greiner, W ;
Davidson, D ;
Rennert, G ;
Barzilai, N .
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2004, 52 (02) :274-277
[6]  
Aviv A., 2004, SCI AGING KNOWLEDGE, V2004, pp, DOI DOI 10.1126/SAGEKE.2004.51.PE43
[7]   Human telomere biology: pitfalls of moving from the laboratory to epidemiology [J].
Aviv, Abraham ;
Valdes, Ana M. ;
Spector, Tim D. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2006, 35 (06) :1424-1429
[8]   Telomere instability in the male germline [J].
Baird, DM ;
Britt-Compton, B ;
Rowson, J ;
Amso, NN ;
Gregory, L ;
Kipling, D .
HUMAN MOLECULAR GENETICS, 2006, 15 (01) :45-51
[9]   Extensive allelic variation and ultrashort telomeres in senescent human cells [J].
Baird, DM ;
Rowson, J ;
Wynford-Thomas, D ;
Kipling, D .
NATURE GENETICS, 2003, 33 (02) :203-207
[10]   The free radical theory of aging matures [J].
Beckman, KB ;
Ames, BN .
PHYSIOLOGICAL REVIEWS, 1998, 78 (02) :547-581