Telomeres are lengths of repeating sequences (TTAGGG) that cap each end of a chromosome. As errors in transcription most commonly at the ends of a chromosome, these caps act as “crumple zones” to protect the coding sequences within from being affected. These caps are shown to shorten over time as the individual ages, Futcher and Greider (1990) was one of the first studies to show a link between aging and shortening of telomeres in vivo humans. This was shown in vivo samples taken from donors varying in age from fatal to 92 years old. This was compared to in vitro fibroblast cell samples which were already known to lose telomere length following replication. The results showed a loss of ~25% of telomere repeats between the youngest and oldest samples. However, it did not account for natural differences in telomere length between any two people of the same age nor how they differ between two different tissues in the same individual. This is an issue that has seen extensive review such as by Cassidy et al (2013). This study examined the natural variance in telomere length between 2284 women who were deemed healthy enough to act as a control group. The study found that length could vary between subjects of the same length. In addition to telomere length the subjects filled in a lifestyle questionnaire regarding diet, exercise, and body mass index. It was found that there was small but significant correlation between telomere length and these factors.
However, age remained the most significant correlation. One factor this study neglects is the role of gender on telomere length. This is the topic researched by Barrett and Richardson (2011) who analyzed existing research in order to address the longevity gap between men and women. The finding revealed a noticeable difference between men and women with men appearing to lose telomere length at a greater rate than women. This resulted in an increased risk of developing a degenerative illness and a shortened life expectancy. This correlates with males generally having a reduced life span compared to women in the UK and elsewhere. In addition, it has been shown that tissues age at different rates (Friedrich 2000). This tissue-specific aging relates to the rate these tissues are replaced with telomeres in rapidly replaced cells like leukocytes in blood noticeably shorter than those in the skin and the synovium. This study of nine elderly patients examined in vivo differences between tissues using PCR. However, this method has been criticized as a method for quantifying the length of telomeres. This is an area that has continued research in both industry and academic institutes to produce new methods for quantifying telomeres without lengthy or expensive sequencing and PCR. An example of this research is Gohring et al (2013) who examined the validity of a new product by Matlab that uses computer software to analyze large numbers of in vivo samples using a biochemical assay. This is not the first such software to do so and Gohring likens it to a previous product known as Telemetric.
The aging effect of telomere shortening is that it results in an increased rate of DNA damage, leading to apoptosis and rapid cell turnover. This effect was reviewed by Sahin and Depinho (2010) which summarized existing research. In particular, they examined the limited number of stem cell divisions and how these can promote common signs of aging associated with degenerative human diseases. They hypothesize that damaged telomeres create a cascade effect whereby damage to telomeres leads to increased p53 activation causing apoptosis and further mutations. The wide range of diseases associated with this mechanism was meta-analyses by Bojesen (2013). This meta-review analyzed dozens of studies in which individual diseases had distinct positive correlation with shortened telomeres. These primarily included degenerative diseases associated with old age such as heart disease, renal failure, and stroke. The study concludes that telomeres could be utilized as a biomarker to assess risk factor. The single largest study in Bojesen’s review was Rode et al (2012) which examined 46,396 members of the population to examine the relationship between telomere length and chronic obstructive pulmonary disease (COPD). The study found noticeable correlation between telomeric length and risk of COPD. However, this wider sample showed less correlation than the smaller more prescriptive samples of earlier studies. A reminder that telomeres are only one risk factor of many that must be taken into account when using telomeres as an indicator for degenerative conditions.
Current research is examining the effect of reversing telomerase destruction. This hypothesis was first trialed by Bodnar et al (1998) who induced telomerase action in normal human cells in vitro. A function most commonly associated with immortal cancerous cells where abnormally lengthened telomeres effectively counter the so-called Hayflick limit. Bodnar et al triggered lengthening in vitro cells by splicing in a new transcription site. While the normal cells expired as predicted around 30 cycles the artificially altered cells survived almost 50 cycles before senescence. Jasekelioff et al (2011) furthered this research by using similar methodology with in vivo adult cells. This was performed using mice selectively bred for shortened telomeres. These mice were genetically engineered at the blast stage to produce telomerase in adulthood. It was found that the mice suffered from advanced aging with notable eutrophication of testes and spleen. It was found when telomerase was reactivated these signs were seen to be reversed (see précis one)