Telomere Length and Aging

Abstract

Telomeres, the TTAGGG tandem repeats at the ends of chromosomes, become progressively shortened with each replication of cultured human somatic cells (reviewed in Wong and Collins (Wong & Collins 2003)) until a critical length is achieved, at which point the cell enters replicative senescence. This situation can be reversed by the enzyme named telomerase that is responsible for Telomere Length maintenance. Activation of the telomerase will result in telomere elongation and regulation of its activity can save the cell from senescence (Zvereva et al., 2010). Though increased activity of telomerase has been noted in cancer cell lines, telomere length could be in steady state suggesting alternative pathways for telomere length maintenance (Ouellette et al. 1999). The length of the telomere is longest at birth and decreases with increasing age. It has been demonstrated in cross-sectional analyses that age affects attrition of Telomere Length in white blood cells (Slagboom et al., 1994; Benetos et al., 2001; Nawrot et al., 2004). The rate of attrition is different between individuals and tissues and is influenced by multiple factors including oxidative stress and activity of telomerase enzyme. Telomere Length reflects the cumulative burden of oxidative stress and repeated cell replication (Serra et al., 2003), and such oxidative stress may represent the link between telomeres and aging-related disease in humans. Telomere shortening has been implicated as a mechanism explaining variations in life expectancy and aging-related diseases. In this chapter we will review the alterations in Telomere Length with aging and its association with multiple age-related diseases. We will discuss the mechanism of telomere shortening and how it is affected by the aging process. Finally we will review the various genetic components that play a part in either telomere attrition or maintenance with aging.