Replicative lifespan

Yang, H., Baur, J. A., Chen, A., Miller, C., Adams, J. K., Kisielewski, A., Howitz, K. T, Zipkin, R. E., Sinclair, D. A. (2007). Design and synthesis of compounds that extend yeast replicative lifespan. Aging Cell, 6, 35-43. 

RPE/Bruch s Membrane Compromised RPE cell functions could seriously jeopardize photoreceptor health. RPE senescence has most widely been studied in the model of replicative senescence. It results from repeated division of the RPE cells in culture (Flood et al., 1980 Burke and Soref, 1988 Sheedlo et al., 1997). These studies have estabhshed a relationship between donor age and the location of the RPE cells (central versus peripheral) and replicative lifespan. There are also studies describing changes in gene expression or the alteration of enzymatic activities during the replicative senescence of RPE cells in vitro (Tombran-Tink et al., 1995). 

Cristofalo V J, Allen R G, Pignolo R J, et al. (1998). Relationship between donor age and the replicative lifespan of human cells in culture a reevaluation. Proc. Natl. Acad. Sci. USA. 95 10614-10619. 

The end of a linear chromosome is called a telomere. Telomeres require a special mechanism, because the ends of a linear chromosome can t be replicated by the standard DNA polymerases. Replication requires both a template and a primer at whose 3 end synthesis begins. The primer can t be copied by the polymerase it primes. What copies the DNA complementary to the primer In a circular chromosome, the primer site is to the 3 direction of another polymerase, but in a linear chromosome, no place exists for that polymerase to bind. As a result, unless a special mechanism for copying the ends of chromosomes is used, there will be a progressive loss of information from the end of the linear chromosome. Two characteristics about telomeres help avoid this situation. First, they consist of a short sequence—for example, AGGGTT—repeated many times at the end of each chromosome. Telomeres, therefore, are part of the highly repetitive DNA complement of a eukaryotic cell. Secondly, a specific enzyme, telomerase, carries out the synthesis of this reiterated DNA. Telomerase contains a small RNA subunit that provides the template for the sequence of the telomeric DNA. Eukaryotic somatic cells have a lifespan of only about 50 doublings, unless they are cancerous. One theory holds that a lack of telomerase in cells outside the germ line causes this limitation. 

Telomerase can compensate the effects of the end replication problems and extend the lifespan of human cells. The enzyme solves these problems by the synthesis and addition of new telomeric repeats to its substrate, the 3 -telomeric... 

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