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Telomers the tandem repetitive DNA sequences located at the ends of human chromosomes.
Telomeres – which are a protective cap at the end of DNA molecules – normally shorten in each replication cycle.
Telomere length is controlled by a group of specialized enzymes, known as telomerase reverse transcriptases.
Telomeres are capping nucleoprotein structures at the end of each chromosome, comprising hexameric tandem repeats of non-coding TTAGGG with 5 to 15 kB length with telomere binding proteins.
Normally, telemere shortens on each round of replication.
Hexanucleotide tandem repeats (TTAGGG) present at the end of chromosomes, protecting them from gradual degradation in the process of aging.
Physiologic telomere losses occur over time, contributing to aging.
Are long tandem nucleotide repeats and an associated protein complex located at chromosome ends that are essential for maintaining chromosomal stability.
Protein bound repetitive DNA sequences that constitute the natural end of linear chromosomes and that protect coding DNA from genetic damage and cells from replicative senescence.
Are DNA protein complexes at the end regions of chromosomes, decreasing length with every cell division.
Once 25-50 divisions pass, the telomeres can be completely lost, inducing p53 to either permanently arrest the cell or induce apoptosis.
Shorten with each cell division due to the inability of DNA polymerases to completely replicate the chromosome ends.
When telomeres become critically short, the ends of chromosomes are exposed as double-stranded DNA brakes, and result in DNA damage, p53 activation, and apoptosis/senescence.
Telomere lengths represent a molecular clock for humans.
Telomere shortening and p53 expression is a key mechanism to prevent uncontrolled replication and tumor development because even cells that excessively proliferate will eventually be inhibited.
Following nearly 1000 humans for ten years showed that while some humans do shorten their telomeres over time, a third of the participants did not.
In cultured human cells, telomere length predicts the finite replicative potential of cells before they senesce,, and the exogenous expression of the teleromase catalytic component TERT can bypass senescence.
The two essential function of telomeres are protecting chromosome ends and facilitates their complete replication.
Telomere length is determined genetically and shortens following each round of cell division, with age and during neoplastic transformation.
TTAGGG DNA repeats at the end of chromosomes.
Are markers of cellular replicative capacity, cellular senescence, and aging.
Short telomeres cause recognizable disease patterns and not generic forms of premature aging.
Mutations in genes that encode telomerase components and other telomere maintenance genes cause disease, referred to as telomere syndromes.
Mutations in 13 telomerase and telomere maintenance genes cause the short telomere syndrome phenotype; and the most common are mutations in TERT.
Gain-of-function TERT mutation up regulates telomerase expression and manifests as familial melanoma, likely related to excessively long telomere length, the long telomere syndrome.
Specialized nucleoproteins at the end of eukaryotic chromosomes.
Consists of 2-15 kb of noncoding tandem repeats of the sequence of TTAGGG.
The end of the telomere is extended by a single stranded 50-300 nucleotide 3’ overhang and by associated proteins that fold into a loop structure.
Maintain the integrity of the chromosome and prevent end to end chromosome fusion breakdown and abnormal recombinations.
In primary blood cells, telomeres are partly reconstructed by telomerase, specialized intracellular enzyme that adds subunit repeats to telomeres.
Telomeres are short in many patients with acquired or inherited aplastic anemia.
Telomerase mutations have been associated with lung fibrosis and cirrhosis and may be a risk factor for cardiovascular disease.
Mindfulness meditation appears to lead to increased telomere length.
Exposure to violence during childhood is associated with shortened telomeres and with reduced telomerase activity: The increased rate of telomere length reduction correlates to a reduction in lifespan of 7 to 15 years.
Short telomere affects patient’s ability to withstand toxicities from routine therapies, especially immunosuppression.
Mutant tellomerase and tellomere genes are the most common cause of inherited bone marrow failure, and recognizing these patients in the hamatpoetic stem cell transplant evaluation alters decisions about the donor and ablative regimens.
Identifying patients with telomere-mediated lung disease may aid in the management of lung transplant, for anticipating and averting complications.
Telomeres and telomerase protect against threats to the genome that arise from asymmetrical replication of DNA.
Without telomeres genetic material would be lost with each cell division.
Regarded as the internal biological clock because they shorten with every cell division.
During somatic cell division, DNA polymerase cannot fully replicate the 3′ end of linear DNA, resulting in a loss of telometric repeats.
Eventually this loss leads to cellular senescence or apoptosis.
In blood cells contain about 10,000-20,000 nucleotides at birth.
Reduces by about 50 bp per year with a reduction to a few thousand bp in the elderly.
Telomere length limits the replicative capacity of tissues and has been implicated in age related disease.
Shorten with each cell cycle and therefore are a reflection of aging at a cellular level.
At a critically short telomere length such cells experience cell senescence.
Malignant cells reactivate and overexpress the enzyme telomerase that lengthens telomeres and allows for further cellular division.
Telomere elongation is common in malignancies.
Critically short telomeres may increase the risk of cancer.
A array of genes is responsible for telomere synthesis, assembly, trafficking, and maintenance.
Defects in one or more of these complex array of genes can cause accelerated telomere shortening and consequently affect multiple organ systems with high cell turnover, resulting in premature graying of hair, interstitial pneumonia, bone marrow failure, cryptogenic cirrhosis, portal hypertension, and immune dysfunction.
Leukocyte telomere length was measured in 787 cancer free individuals and followed for 10 years: short telomere at baseline was associated with increased cancer incidence and mortality (Williet P).
Short telomere linked with bladder cancer, renal cell cancer, non-Hodgkin’s lymphoma, lung cancer and head and neck tumors.
Patients with short telomere-related disease are prone to increase toxicities from otherwise routine therapies, especially immunosuppression.
Unanticipated teleromasevs and telomere genes aew the most common cause of inherited bone marrow failure, and recognizing these patients in the hematopoietic stem cell transplant evaluation alters decisions about the donor and ablative regimens.
Telomere shortening in white blood cells is implicated for immunocompetence and is associated with increased synthesis of proinflammatory cytokines and poorer antibody response to vaccination.
Shorter leukocyte telomere length is associated with age-related morbidity and mortality from conditions with immune systems involvement, including cancer, cardiovascular disease, and infectious diseases.
The rate of progression to senescence among lymphocyte subsets vary, and the advanced rate of telomere shortening in cytolytic CD8 T cells result loss of expression of CD 28, a costimulatory molecule important for antiviral function.
In healthy 18-55 years old shorter CD8C28 T-cell telomere length is associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness (Cohen S et al).
Leukocyte telomere length is a predictor of early onset of aging related morbidity and mortality in older adults.
Telomere length is important in age-related functional decline and development of chronic disease.
In children and young adults a severe form of short telomere syndrome manifest as bone marrow failure, immuno deficiency, and abnormalities in the skin and G.I. tract and is associated with high tissue turn over.
Adult-onset disease accounts for more than 90% of short telomere syndrome presentations represents an attenuated form of the short telomeres syndrome phenotype.
Short telomere syndrome is common in lung disease, predominantly in idiopathic pulmonary fibrosis and related interstitial disease is as well as emphysema.
Pulmonary fibrosis shows autosomal dominant inheritance in approximately1/3 of patients with familial clustering carymutations in telomerase and telomere-maintenance genes.
Telomere genetics explains a subset of susceptibility of familial and sporadic idiopathic pulmonary fibrosis.
There are no current therapies that lengthen telomeres.
Telomeres are essential to protect it from chromosome end-to-end fusion, nucleolytic decay, attacked by DNA repair enzymes at double stranded breaks, and aberrant recombination to maintain chromosome integrity and genomic debility.
Telomere length is maintained by the enzyme telomerase, which is overexpressed in germ cells and neoplastic tissue.
In most eukaryotic tissue telomerase expression may prevent telomere erosion.
Telomeres in blood cells contain about 10,000-20,000 nucleotides at birth.
Telomeres reduces by about 50-150 bp per year with a reduction to a few thousand bp in the elderly.
Gerline mutations that impact the telomere complex can lead to loss of telomeres during cell replication, shortening the stem cell pool.
Regeneration stresses that occur in patients with bone marrow failure, chemotherapy, or hematopoetic stem cell transplant can enhance telomere shortening secondary to increased mitotic activity.
2 replies on “Telomeres”
Understanding what causes telomere lengthening in melanoma will undoubtedly pave the way for the commercial promotion of products that claim to lengthen telomeres to reverse or prevent ageing.
But while telomeres are interesting, they don’t really explain much.
I think the closest we have seen to reversing and/or stopping ageing are the well-known parabiosis experiments mentioned by Harold Katcher in his 2013 paper, which seem to form the basis of his recent work to develop a blood-based ‘elixir’ that can actually stop and/or reverse ageing.
The experiments Harold mentions (younger mice joined to an older mouse) show that something in the blood supply makes older mice younger, and vice versa (possibly the reduction of TGF-b1 and the increase of oxytocin). Similar results occur when old tissue is transplanted into younger mice: the old tissue becomes young again. This seems to me to be the real solution and I can’t wait to find more studies on this. 🙂
Thank you for your input.