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.

Nanodelivery of Natural Antioxidants: An Anti-aging Perspective

“…Telomeres are nucleotide repeated sequences of eukaryotic linear chromosomes that cap the chromosome ends to protect from undesirable enzymatic activities. In absence of specific enzymatic activity of telomerase, telomeres shorten with every cell division, being thereby substantially involved in aging processes (Hayashi, 2018;Liu et al, 2019). Emerging evidence, however, indicates the age-related telomere shortening depends not only on the number of divisions that cells have undergone, but also on the level of oxidative stress (Koliada et al, 2015).…”

Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

“…In mammals, many nucleoproteins collectively termed as "shelterin" complex (TRF1, TRF2, TIN2, RAP1, POT1, and TPP1) coat the telomeric DNA and protect the chromosome ends. In yeast, the "shelterin" complex constitutes three complexes, Ku70-Ku80 complex, Rap1-Rif1-Rif2 complex, and Cdc13-Stn1-Ten1 (CST) complex, which function cooperatively at telomeric repeats [184]. The DNA damage repair protein Ku is composed of Ku70 and Ku80 heterodimers, which directly associate with telomeres in both mammals and yeast and maintain chromosome integrity.…”

Identifying Longevity Associated Genes by Integrating Gene Expression and Curated Annotations

“…Depletion of ribosomes is known to increase lifespan (Steffen et al, 2008), so a negative coefficient for chromatin silencing at rDNA is appropriate. Telomeres are known to be important in yeast longevity (Austriaco & Guarente, 1997;Liu, Wang, Wang, & Liu, 2019), so a large coefficient for telomere maintenance makes sense. Longevity effects of cellular response to oxidative stress are corroborated in the literature (Postnikoff, Johnson, & Tyler, 2017).…”