Telomeres are nucleoprotein structures that cap the ends of chromosomes, maintain chromosome stability and prevent end-to-end fusion of chromosomes during cell division. Degradation of telomeres has been shown to lead to whole chromosomal instability, an important risk factor for cancer (6, 7). Telomere shortening has also been proposed as one of the fundamental mechanisms that determine the rate of aging in cells (8, 9). Studies indicate that folate and nicotinic acid deficiencies together with increased oxidative stress may accelerate telomere dysfunction. Such metabolic imbalances may possibly explain the observed associations between telomere shortening and a number of conditions including obesity, psychological stress, immune dysfunction, cancer and cardiovascular disease (10-15).
Under folate-deficient conditions the base uracil is incorporated into DNA instead of thymidine, leading to chromosome breakage. In addition, folate and vitamin B12 play a critical role in maintenance of DNA methylation which, apart from its importance for transcriptional control of gene expression, determines the structural stability of important regions of the chromosomes. There is strong evidence that defects in the DNA methylation process can cause excessive telomere dysfunctions (16). It is therefore possible that deficiency of folate and other methyl donors may also result in telomere instability by causing inadequate maintenance of methylation. Nicotinic acid (niacin) is another dietary micronutrient that is known to play a fundamental role in chromosome integrity and reduction of cancer risk (17, 18).
Damage to DNA, lipids and proteins induced by reactive oxygen species may be controlled by antioxidants (such as vitamins C and E) as well as enzymic mechanisms such as superoxide dismutase and catalase (19). Under certain conditions, such as increased levels of free radicals and/or reduced levels of antioxidants, an imbalance can occur and the capacity for prevention and repair can become overwhelmed. In in-vitro studies antioxidant treatment has been found to prevent telomere attrition and to increase cellular lifespan (20); however, whether similar effects can be achieved in vivo remains uncertain.