Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes

Journal Article · Thu Apr 01 04:00:00 EST 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6333499

Vaziri, H; Uchida, I; Wei, Lan; Harley, C B ^[1]; Schaechter, F; Cohen, D ^[2]; Zhu, Xiaoming; Effros, R ^[3]

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1. McMaster Univ., Hamilton, Ontario (Canada)
2. Centre d'Etude du Polymorphisme Humain, Paris (France)
3. Univ. of California, Los Angeles (United States)

The telomere hypothesis of cellular aging proposes that loss of telomeric DNA (TTAGGG) from human chromosomes may ultimately cause cell-cycle exit during replicative senescence. Since lymphocytes have a limited replicative capacity and since blood cells were previously shown to lose telomeric DNA during aging in vivo, the authors wished to determine (a) whether accelerated telomere loss is associated with the premature immunosenescence of lymphocytes in individuals with Down syndrome (DS) and (b) whether telomeric DNA is also lost during aging of lymphocytes in vitro. To investigate the effects of aging and trisomy 21 on telomere loss in vivo, genomic DNA was isolated from peripheral blood lymphocytes of 140 individuals (age 0--107 years), including 21 DS patients (age 0--45 years). Digestion with restriction enzymes HinfI and RsaI generated terminal restriction fragments (TRFs), which were detected by Southern analysis using a telomere-specific probe ([sup 32]P-(C[sub 3]TA[sub 2])[sub 3]). The rate of telomere loss was calculated from the decrease in mean TRF length, as a function of donor age. DS patients showed a significantly higher rate of telomere loss with donor age (133 [+-] 15 bp/year) compared with age-matched controls (41 [+-] 7.7 bp/year) (P < .0005), suggesting that accelerated telomere loss is a biomarker of premature immunosenescence of DS patients and that it may play a role in this process. Telomere loss during aging in vitro was calculated for lymphocytes from four normal individuals, grown in culture for 10--30 population doublings. The rate of telomere loss was [approximately]120 bp/cell doubling, comparable to that seen in other somatic cells. Moreover, telomere lengths of lymphocytes from centenarians and from older DS patients were similar to those of senescent lymphocytes in culture, which suggests that replicative senescence could partially account for aging of the immune system in DS patients and in elderly individuals. 31 refs., 3 figs.

• OSTI ID: 6333499
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:4; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CYCLE
CHROMOSOMES
CONGENITAL DISEASES
CONGENITAL MALFORMATIONS
CONNECTIVE TISSUE CELLS
DISEASES
DNA
DNA HYBRIDIZATION
DOWNS SYNDROME
HEREDITARY DISEASES
HUMAN CHROMOSOME 21
HUMAN CHROMOSOMES
HYBRIDIZATION
IN VITRO
IN VIVO
LEUKOCYTES
LIFE SPAN
LOSSES
LYMPHOCYTES
MALFORMATIONS
MAMMALS
MAN
MATERIALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PRIMATES
SOMATIC CELLS
VERTEBRATES