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Telomeres and Telomerase02:41

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Telomeres and Telomerase02:41

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In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
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In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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Monochrome Multiplex Quantitative PCR Telomere Length Measurement
11:44

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Published on: March 22, 2024

Leukocyte telomere dynamics in the elderly.

Troels Steenstrup1, Jacob V B Hjelmborg, Laust H Mortensen

  • 1Department of Biostatistics, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

European Journal of Epidemiology
|February 23, 2013
PubMed
Summary

In elderly individuals, leukocyte telomere length (LTL) generally shortens with age. Apparent LTL elongation in some older adults is likely due to measurement error, not true biological change.

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Area of Science:

  • Gerontology
  • Molecular Biology
  • Genetics

Background:

  • Limited data suggest leukocytes in the elderly have ultra-short telomeres.
  • Some studies report age-dependent elongation of leukocyte telomere length (LTL) in elderly individuals.
  • Understanding LTL dynamics in aging is crucial for gerontological research.

Purpose of the Study:

  • To characterize leukocyte telomere length (LTL) dynamics in elderly individuals using cross-sectional and longitudinal models.
  • To investigate the phenomenon of apparent LTL elongation in aging populations.
  • To determine the relationship between telomere length distribution and aging.

Main Methods:

  • Utilized the Longitudinal Study of Aging Danish Twins cohort.
  • Measured leukocyte telomere length (LTL) via Southern blot of terminal restriction fragment length (TRFL).
  • Employed both cross-sectional analysis (n=476, ages 73-94) and longitudinal follow-up (n=80, ~10 years).

Main Results:

  • Average LTL attrition rate was 27 bp/year (cross-sectional) and 31 bp/year (longitudinal).
  • Females exhibited significantly longer mean TRFL than males by 180 bp.
  • Observed a shift in TRFL distribution towards shorter telomeres with age; apparent LTL elongation in ~7.5% of individuals was consistent with measurement error.

Conclusions:

  • The accumulation of ultra-short telomeres in elderly leukocytes reflects a shift in the overall telomere length distribution towards shorter lengths.
  • Measurement error is the probable explanation for observed leukocyte telomere length (LTL) elongation in longitudinal aging studies.
  • LTL attrition is a significant factor in aging, with potential sex differences.