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A telomere (/ ˈ t ɛ l ə m ɪər, ˈ t iː l ə-/; from Ancient Greek τέλος (télos) 'end' and μέρος (méros) 'part') is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes.
When telomeres reach a critically short length, sufficient shelterin proteins to inhibit checkpoint activation are not available, although NHEJ and HR generally remain inhibited at this point. [5] This loss of inhibition is one reason why telomere shortening causes senescence (Figure 1B).
Telomere dysfunction during cellular aging (a state in which cells do not divide but are metabolically active) affects the health of the body. [2] Preventing telomere shortening without clearing old cells may lead to the accumulation of these cells in the body and contribute to age-related diseases and tissue dysfunction. [29]
Telomere shortening does not occur with age in some postmitotic tissues, such as in the rat brain. [35] In humans, skeletal muscle telomere lengths remain stable from ages 23 –74. [ 36 ] In baboon skeletal muscle, which consists of fully differentiated postmitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage ...
The successive shortening of the chromosomal telomeres with each cell cycle is also believed to limit the number of divisions of the cell, contributing to aging. After sufficient shortening, proteins responsible for maintaining telomere structure, such as TRF2, are displaced, resulting in the telomere being recognized as a site of a double ...
The typical normal human fetal cell will divide between 50 and 70 times before experiencing senescence. As the cell divides, the telomeres on the ends of chromosomes shorten. The Hayflick limit is the limit on cell replication imposed by the shortening of telomeres with each division. This end stage is known as cellular senescence.
Alternative Lengthening of Telomeres (also known as "ALT") is a telomerase-independent mechanism by which cancer cells avoid the degradation of telomeres.. At each end of the chromosomes of most eukaryotic cells, there is a telomere: a region of repetitive nucleotide sequences which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes.
Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks.