Roles of Telomere Biology in Cell Senescence, Replicative and Chronological Ageing

Abstract

Telomeres with G-rich repetitive DNA and particular proteins as special heterochromatin structures at the termini of eukaryotic chromosomes are tightly maintained to safeguard genetic integrity and functionality. Telomerase as a specialized reverse transcriptase uses its intrinsic RNA template to lengthen telomeric G-rich strand in yeast and human cells. Cells sense telomere length shortening and respond with cell cycle arrest at a certain size of telomeres referring to the "Hayflick limit." In addition to regulating the cell replicative senescence, telomere biology plays a fundamental role in regulating the chronological post-mitotic cell ageing. In this review, we summarize the current understandings of telomere regulation of cell replicative and chronological ageing in the pioneer model system Saccharomyces cerevisiae and provide an overview on telomere regulation of animal lifespans. We focus on the mechanisms of survivals by telomere elongation, DNA damage response and environmental factors in the absence of telomerase maintenance of telomeres in the yeast and mammals.

Keywords: ageing; chronological ageing; lifespan; replicative ageing; senescence; telomere; yeast.

Figure 1

Roles of telomere biology in cell senescence, replicative and chronological ageing. Cells evolve to have regulated telomerase activity to preserve telomere homeostasis which is vital to genome stability in organism ageing. Short telomeres are maintained by telomerase in the early stage, telomere DNA homologous recombination or subtelomeric DNA amplification in the late stage of telomere shortening. Telomerase inactivation results in critically short telomeres that either activate the cell cycle check-point resulting in cell senescence or promote telomere-telomere recombination or subtelomere amplification resulting in genome instability and replicative difficulty. Long telomere associated genome instability and replicative difficulty cause not only telomere shortening but also non-telomeric damages, culminating in cell senescence, replicative ageing and accelerated chronological ageing.