Telomerase Shortening Associated with Cellular Aging
Strcuture and Function of Telomeres
A eukaryotic chromosome consists of a long strand of DNA. At the terminal end of each chromosome is a telomere. It is made up of a continuous repeats of DNA sequence and associated proteins. In case of humans and other vertebrates, telomeric DNA sequence consists of 5’(TTAGGG)3’, which is pointed towards the end of one DNA strand with the complimentary strand 5’(CCCTAA)3’ – pointed towards the interior of the chromosome. It has been found that telomeric DNA is associated with a large number of proteins such as RF1, TRF2, TIN2, TPP1, Rap1, and POT1. In addition, there is a specialized reverse transcriptase enzyme called telomerase, which is capable of extending the 3’ end of chromosomes.
Chromosome ends are vital for chromosome stability – Barbara McClintock proposed chromosome stability for the first time in the 1930’s while working with maize. Hermann Muller drew the same conclusion while working with fruitflies. Muller coined the term telomere. McClintock, on the other hand, pointed out that without these terminal structures, chromosomes would fuse or break during mitosis. Thus telomere protects chromosome ends and provides stability and also ensures precise segregation of genetic material into daughter cells during cell division.
Telomeres and Aging
Aging is one of the complex processes that occur on various levels. The final result of aging is the life span limitation in multicellular organisms. The cells that are associated with multicellular organisms also have restricted life spans. The restriction could be comprised of two fundamental parts: 1. Cells cease to divide but remain active metabolically, 2. Cell death occurs. There are several cells in the human body that undergo cellular division. It is a normal condition of several tissues, example: hair growth. In several instances, cellular division takes place to heal damaged tissues. Thus, with limited number of cell division, it could contribute to aging by slowing down the processes such as tissue maintenance and wound healing, etc.
Chromosomes are long strands of DNA. At the end of each chromosome, there is a specialized structure called telomeres. It keeps the chromosome protected and also prevents them from fusing with other DNA molecules. In addition, telomeres play a vital role in cell division. During each cell division, DNA replication takes place where a new DNA strand is formed from the template. However, some terminal part of the DNA may not be replicated due to the limited amounts of telomerase enzyme unlike unicellular eukaryotes that possess unlimited amounts of telonerase enzyme, and therefore, the telomeres get shorten with each cycle of cell division. This mechanism then limits propagation of human cells to a restricted number of cell divisions by including replicative senescence, differentiation, or apoptosis. Short telomeres can cause several disorders including dyskeratosis congenita, aplastic anemia, and cancer besides others.
Additionally, telomerase shortening is also enhanced by the action of nucleases or other DNA damaging agents. Surprisingly, telomerase abrasion has been seen with increasing age in human tissues where it has been experimentally tested. This reveals that amass cell divisions are linked with tissue renewal. There are several age related pathologies and early aging syndromes, which are described by a faster-than-normal rate of telomere shortening that put forwards that telomere shortening may be the reason of organismal aging.
(Web): Telomere length, stem cells and aging – https://clarke.physics.uwo.ca/JournalClubPDF/JCArchives/telomere.pdf
(Web): Telomeres and Aging – https://physrev.physiology.org/cgi/content/full/88/2/557
(Web): Cellular Aging: Telomeres - Telomere Structure – https://medicine.jrank.org/pages/278/Cellular-Aging-Telomeres-Telomere-structure.html