positive regulation of telomere maintenance via telomere lengthening

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of telomere maintenance via telomere lengthening. [GO_REF:0000058, GOC:BHF, GOC:BHF_telomere, GOC:nc, GOC:TermGenie, PMID:23959892]

Positive regulation of telomere maintenance via telomere lengthening is a crucial biological process that ensures the stability and integrity of chromosomes, thereby promoting cellular longevity and preventing premature aging. Telomeres are protective caps at the ends of chromosomes, preventing degradation and fusion of DNA. With each cell division, telomeres naturally shorten due to the inability of DNA polymerase to fully replicate the ends of linear chromosomes. This gradual shortening contributes to cellular senescence, a state of irreversible cell cycle arrest, and ultimately, aging. However, some cells, such as stem cells and germ cells, possess mechanisms to counteract telomere shortening and maintain their replicative capacity.

Telomere lengthening, also known as telomere elongation, is the process of extending the length of telomeres. It is primarily achieved through the action of the enzyme telomerase, a reverse transcriptase that synthesizes repetitive DNA sequences (TTAGGG in humans) at the ends of chromosomes. Telomerase is a ribonucleoprotein complex consisting of a catalytic protein subunit (TERT) and a template RNA subunit (TERC). TERC acts as a template for the synthesis of the telomeric repeats, while TERT possesses the reverse transcriptase activity to extend the telomere using TERC as a guide.

The process of positive regulation of telomere maintenance via telomere lengthening involves a complex interplay of factors, including:

- **Telomerase expression and activity:** The expression and activity of telomerase are tightly regulated in different cell types. Stem cells and germ cells exhibit high levels of telomerase, allowing them to maintain telomere length and proliferate indefinitely. However, in most somatic cells, telomerase activity is suppressed, leading to gradual telomere shortening with each cell division.

- **Transcriptional and post-transcriptional regulation of telomerase:** The expression of telomerase is regulated at both the transcriptional and post-transcriptional levels. Transcription factors, such as MYC, c-MYB, and Sp1, can bind to the promoter region of the TERT gene, enhancing its transcription. Post-transcriptional regulation of telomerase involves factors like microRNAs and other regulatory proteins that can modulate its stability and translation.

- **Telomere binding proteins:** A variety of proteins, including shelterin complex components, bind to telomeres, contributing to their stability and regulating access to the telomere by telomerase. These proteins play crucial roles in protecting telomeres from degradation and promoting the recruitment of telomerase.

- **Cellular signaling pathways:** Several signaling pathways, including the PI3K/AKT pathway, MAPK pathway, and Wnt pathway, can modulate telomere length and telomerase activity. These pathways are influenced by various stimuli, including growth factors, stress, and cellular environment.

- **Environmental factors:** External factors like diet, exercise, and exposure to toxins can indirectly influence telomere maintenance through their effects on cellular signaling pathways and telomerase activity.

Dysregulation of telomere maintenance can have profound consequences. Excessive telomere lengthening can lead to uncontrolled cell proliferation and cancer development. Conversely, insufficient telomere lengthening can contribute to premature aging and age-related diseases. Understanding the complex mechanisms of telomere maintenance and regulation is crucial for developing strategies to combat aging and age-related diseases, promote cellular longevity, and potentially prevent cancer.'
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Proteins (1)

Compounds (20)