:
Telomeres are the protective end caps of eukaryotic chromosomes and they decide the
proliferative lifespan of somatic cells, as the guardians of the cell replication. Telomere length in
leucocytes reflects telomere length in other somatic cells. Leucocyte telomere length can be a
biomarker of human ageing. The risk of diseases, which are associated with reduced cell
proliferation and tissue degeneration, including aging or aging-associated diseases, such as
dyskeratosis congenita, cardiovascular diseases, pulmonary fibrosis and aplastic anemia, are
correlated with an increase in short telomeres. On the other hand, the risk of diseases, which are
associated with increased proliferative growth, including major cancers, is correlated with long
telomeres. In most of the cancers, a telomere maintenance mechanism during DNA replication is
essential. The reactivation of the functional ribonucleoprotein holoenzyme complex [telomerase]
starts the cascade from normal and premalignant somatic cells to advanced malignant cells.
Telomerase is overexpressed during the development of cancer and embryonic stem cells, through
controlling genome integrity, cancer formation and stemness. Cancer cells have mechanisms to
maintain telomeres to avoid initiation of cellular senescence or apoptosis, and halting cell division
by critically short telomeres. Modulation of the human telomerase reverse transcriptase is the ratelimiting step for the production of functional telomerase and the telomere maintenance. Human
telomerase reverse transcriptase promoter promotes its gene expression only in tumor cells, but
not in normal cells. Some cancers activate an alternative lengthening of telomeres maintenance
mechanism via DNA recombination to unshorten their telomeres. Not only heritability but also
oxidative stress, inflammation, environmental factors, and therapeutic interventions have an effect
on telomere shortening, explaining the variability in telomere length across individuals. There have
been a large number of publications, which correlate human diseases with progressive telomere
shortening. Telomere length of an individual at birth is also important to follow up telomere
shortening, and it can be used as biomarkers for healthy aging. On the other hand, understanding
of cellular stress factors, which affect stem cell behavior, will be useful in regeneration or treatment
in cancer and age-associated diseases. In this review, we will understand the connection between
stem cell and telomere biology, cancer, and aging-associated diseases. This connection may be
useful for discovering novel drug targets and improve outcomes for patients having cancer and
aging-associated diseases.
The CDKN2A G500 Allele Is More Frequent in GBM Patients with No Defined Telomere Maintenance Mechanism Tumors and Is Associated with Poorer Survival
