Telomere Length as Potential Metal Exposure Biomarker: State of the Art and Perspectives

Telomeres are terminal parts of linear chromosomes consisting of repeated nucleotide sequences and six proteins termed shelterin complex that caps telomeric DNA from degradation [1]. Telomere shortening occurs with each mitotic cycle, due to the end replication problem [2]. The reduction of telomere length may be counteracted by telomerase, an enzyme consisting of RNA subunit and catalytic subunit telomerase reverse transcriptase (TERT), which elongates telomeric DNA. Alternative telomere lengthening may also occur due to recombination-based DNA replication [3]. Concomitantly, telomerase is active only in actively dividing cells like germ or cancer cells, whereas in differentiating cells its expression is down-regulated. Therefore, somatic cells have a predetermined number of divisions subsequently [4]. When telomeres are shortened to a critical length, the cell becomes senescent and dysfunctional and undergoes apoptosis. The rate of telomere shortening has increased in aging and a number of age-related diseases [5].