Telomerase and the aging process

Abstract

The level of telomerase activity is important in determining telomere length in aging cells and tissues. Here evidence on the importance of telomerase activity is reviewed with respect to aging rates of mammalian species and the health and life span of individuals within a species. The significance of telomerase reactivation for both cancer development and for immortalizing cells for therapeutic processes is assessed. KeywordsTelomerase; telomeres; senescence; cancer; immortalization Telomeres are the specialized repetitive DNA sequences at the ends of the linear chromosomes, and associated proteins, that serve to maintain the integrity of the chromosomes. Telomerase is a ribonucleoprotein DNA polymerase complex that maintains telomere length. The complex comprises the protein telomerase reverse transcriptase (TERT, or hTERT in humans) and a catalytic RNA (TERC) (Shay and Wright, 2007). In the absence of telomerase activity telomeres progressively shorten. Telomerase activity is absent in most normal human somatic cells because of the lack of expression of TERT; TERC is usually present. On the other hand most mouse cells have telomerase activity (Blasco, 2005). Without telomerase, telomere shortening eventually limits the growth of cells, either by senescence, in cells with intact cell cycle checkpoints (a G1 cell cycle block), or by crisis in cells with inactivated checkpoints (telomeric end-to-end fusions cause chromosome breakage and mitotic catastrophe) (Shay and Wright, 2007). Expression of TERT in cells that otherwise lack telomerase activity causes cells to bypass senescence and crisis, and such cells are usually termed "immortalized." The significance of senescence, crisis and immortalization is explored further in this revew (see Figure 1). Do telomere biology and telomerase activity determine aging?The first aspect to this question is whether differences in aging rates among mammalian species are caused in whole or in part by species-specific differences in telomerase/telomere biology. A very brief consideration of this question will show that this is unlikely. Mice are short-lived compared to humans, yet mice have long telomeres and adult mouse somatic cells often have telomerase activity (Blasco, 2005). On the other hand, humans have relatively short telomeres, even when compared to closely related primates (Kakuo et al., 1999), and telomerase activity

Dynamics of telomere length in captive Siamese cobra (Naja kaouthia) related to age and sex

“…Similar age-related telomere length sex differences were also found in water pythons and other vertebrates (Barrett & Richardson, 2011;Jemielity et al, 2007;Ujvari & Madsen, 2009), indicating a relationship between high mortality and telomere maintenance in somatic cells resulting in shorter life span (Hornsby, 2007;Kirkwood, 1977;Tricola et al, 2018). Similar age-related telomere length sex differences were also found in water pythons and other vertebrates (Barrett & Richardson, 2011;Jemielity et al, 2007;Ujvari & Madsen, 2009), indicating a relationship between high mortality and telomere maintenance in somatic cells resulting in shorter life span (Hornsby, 2007;Kirkwood, 1977;Tricola et al, 2018).…”

Hematopoietic lineage skewing and intestinal epithelia degeneration in aged mice with telomerase RNA component deletion

“…Telomerase activity is an important determinant of telomere length in mammalian cells, in which lack of telomerase activity could exacerbate cell senescence, especially in highly proliferative tissues (Al-Ajmi et al, 2014; Hornsby, 2007; Richardson et al, 2014). Telomerase mutation and the associated telomere shortening had been characterized as causative factors for human diseases (Calado et al, 2009; Young, 2012), such as liver cirrhosis (Calado et al, 2011; Hartmann et al, 2011), pulmonary fibrosis (Armanios et al, 2007; Cronkhite et al, 2008; Tsakiri et al, 2007; Tsang et al, 2012), and bone marrow (BM) failure (Armanios et al, 2005; Heiss et al, 1998; Ly et al, 2005; Vulliamy et al, 2004; Yamaguchi et al, 2003; Yamaguchi et al, 2005).…”

Podocyte dysfunction in aging - related glomerulosclerosis

“…Oxidative stress shortens telomeres (94) and telomere have been shown to shorten in kidney with age (95). Tolemeres are specialized repetitive DNA sequences at the end of the linear chromosomes that serve to mantain the integrity of the chromosomes (96). Telomerase is a ribonucleoprotein DNA polymerase complex that mantains telomere length.…”