**6. Conclusion**

The observed associations reported in this chapter between telomere length and the risk of many different diseases suggest that telomeres play a fundamental role in health both at cells and organism levels. **Figure 1** summarizes some aspects that could influence telomere length. Nevertheless, for several of those diseases it is not clear if telomere length is itself the cause or consequence. For many cancers, though, telomere length shortening seems to be a major cause for triggering oncogenesis through genomic instability. It is recognized that telomeres shorten with age, but also that other factors may accelerate this process, or even reverse it in an unhealthy manner. Both occupational and environmental exposure to toxic agents has been shown to modify telomere dynamics. At the same time, telomere length has emerged as a biomarker for studies analyzing this kind of exposure. Interventions aimed at increasing telomere length proposing to reverse the ageing process or preventing diseases have obtained strong evidence but are not yet enough. On the other hand, it is clear that dietary factors are associated with telomere maintenance in humans. Considering molecular and cellular mechanisms by which telomere dynamics can be modified, it is evident that epigenetic status, mainly DNA methylation, and oxidative stress are strongly involved. Oxidative damage appears to be the main condition that can destabilize telomere dynamics. We still have a long way to go trying to figure out all the particularities of telomere maintenance. The current challenge for researchers is to include other markers and analysis beyond the telomere length to further understand its mechanism and elucidate telomere biology and its influence on human health.

**Figure 1.** Graphical representation of factors that influence telomere length in different aspects.

### **Acknowledgements**

vitamin preparations are characterized by 273 bp longer telomeres than those who are not treated [115]. Vitamins C and E have also shown associations with longer telomeres [115]. It is relevant that both ascorbic acid (vitamin C) and tocopherol (vitamin E) are recognized antioxidants [116–119] that can prevent ROS generation, therefore increasing oxidative stress. For patients with Alzheimer's disease, elevated oxidative stress levels were found, besides shorter telomeres [120]. When vitamin E was administered to these patients, although there was no significant difference in telomere length after 6 months, levels of oxidative stress were

Iron is a biologically very important trace element for maintaining metabolic homeostasis and genome stability. Nevertheless, it is required in a relatively narrow range, otherwise iron becomes a high potential generator of ROS [121]. Iron catalyses the Fenton reaction by generating the 8‐hydroxy‐guanine adduct, one of the most common DNA oxidative damages [13], found also in telomeres [17]. Iron overload induces DNA hypermethylation and can shorten telomere length [122], although the relationship between iron status and telomere dynamics is not totally clear. Shortened telomeres were found in patients with primary hematochromatosis and in patients taking supplements containing iron [123]. In women using iron preparations, telomeres were shortened by 9% when compared to non‐users [115].

A low fat diet has also been associated with improvements in telomere dynamics. Men with prostate cancer who changed their lifestyle to a low fat diet, increased activity and stress reduction, presented increased peripheral blood mononuclear cells telomerase activity [124]. Also, polyunsaturated fatty acid intake was inversely associated with telomere length after multivariate adjustment in a group of 2284 American women [125]. The practice of physical exercise is well known as an important resource for a healthier life. Considering its effect on telomere length, some studies have reported no effect at all. One study observed a significant moderating effect of vigorous physical activity in protecting telomeres against cellular stress in women [126]. Endurance exercises were also relevant for older athletes. When compared to individuals of the same age, but low levels of exercise, older athletes had longer telomere length. Yet, among younger athletes, this difference was not observed regardless of endurance or practicing lower levels of exercise [106]. This result suggests that the lifetime practice of

The observed associations reported in this chapter between telomere length and the risk of many different diseases suggest that telomeres play a fundamental role in health both at cells and organism levels. **Figure 1** summarizes some aspects that could influence telomere length. Nevertheless, for several of those diseases it is not clear if telomere length is itself the cause or consequence. For many cancers, though, telomere length shortening seems to be a major cause for triggering oncogenesis through genomic instability. It is recognized that telomeres shorten with age, but also that other factors may accelerate this process, or even reverse it in an unhealthy manner. Both occupational and environmental exposure to toxic agents has been

exercises might help the slower shortening of telomere length.

lower [120].

174 Telomere - A Complex End of a Chromosome

**6. Conclusion**

All our studies involving telomere length and occupational exposure received financial support from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPERGS (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul) and ULBRA (Lutheran University of Brazil), Brazil.
