CYTOGENETIC INVESTIGATION OF TELOMERE DYSFUNCTION IN PREMATURE AGING SYNDROMES AND DISORDERS

Abstract

Background: Telomeres are structures on chromosomes that protect chromosomes and regulate cell lifespan and genomic stability. Progressive telomere shortening and dysfunction are prominently implicated in premature aging syndromes such as Hutchinson–Gilford Progeria Syndrome, Werner syndrome and dyskeratosis congenita. The cytogenetic abnormalities of telomere instability induce increased cellular senescence, accumulation of damage to DNA and pathological conditions of aging.

Objective: This work is devoted to telomere dysfunction and chromosomal instability of premature aging syndromes by advanced cytogenetic and molecular analysis methods.

Methods: Peripheral blood lymphocytes, fibroblast cultures and stem cells obtained from patients were compared by cytogenetic analysis. Fluorescence in situ hybridization (FISH), quantitative PCR (qPCR), immunofluorescence imaging and chromosomal karyotyping were used to assess telomere length, telomerase activity and genomic instability.

Results: Dyskeratosis congenita patients had telomeres about 50% shorter than healthy controls and progeria syndrome patients had a 45% higher rate of chromosomal instability than healthy controls. Molecular analysis revealed upregulated expression of senescence markers and decreased telomerase activity in all premature aging disorders.
Conclusion: Advanced cytogenetic and molecular approaches greatly improve the detection of telomere dysfunction and chromosomal instability, which will support future diagnostic and therapeutic advances in premature aging syndromes.