Telomere dynamics: the influence of folate and DNA methylation

Abstract

Since the suggestion of their existence, a wealth of literature on telomere biology has emerged aimed at solving the DNA end-underreplication problem identified by Olovnikov in 1971. Telomere shortening/dysfunction is now recognized as increasing degenerative disease risk. Recent studies have suggested that both dietary patterns and individual micronutrients-including folate-can influence telomere length and function. Folate is an important dietary vitamin required for DNA synthesis, repair, and one-carbon metabolism within the cell. However, the potential mechanisms by which folate deficiency directly or indirectly affects telomere biology has not yet been reviewed comprehensively. The present review summarizes recent published knowledge and identifies the residual knowledge gaps. Specifically, this review addresses whether it is plausible that folate deficiency may (1) cause accelerated telomere shortening, (2) intrinsically affect telomere function, and/or (3) cause increased telomere-end fusions and subsequent breakage-fusion-bridge cycles in the cell.

Increased Telomere Attrition After Renal Transplantation—Impact of Antimetabolite Therapy

“…45 The link between higher folate and greater telomere attrition may appear counterintuitive because a decrease in folate has been associated with genomic instability. 17,19,21,23 However, it has also been reported that elevated folate stimulates cell division, 45 which could increase telomere attrition through its involvement in nucleotide synthesis. Indeed, Paul et al 46 have reported decreasing telomere length with increasing folate, and a recent study has shown that folate deficiency results in telomere elongation.…”

“…Although reports in the literature appear contradictory, homocysteine, folate and telomere attrition are consistently associated with each other. 21-24,45-47 Thus, the relationship between them should be investigated more thoroughly, preferably in cohorts undergoing premature aging, such as CKD patients.…”

Telomere Length and Its Relation to Human Health

“…Plasma homocysteine concentration, which is increased when folate and vitamin B12 are deficient, seems to be inversely associated with telomere length. On the other hand, homocysteine and folate are inversely correlated [109]. Low levels of folate were associated with shorter telomeres in an older male cohort, although this effect was not observed either in female subjects or younger adults [108].…”

Frequência genotípica em amostras de MTHFR para o polimorfismo C677T em pacientes da cidade de Curitiba-PR

“…Estudos realizados por Supic et al (17) e Sailasree et al (15) demonstraram que essa mutação aliada ao consumo de álcool é responsá-vel pelo aumento de câncer bucal e câncer de mama em mulheres (10) . Pode também estar associada a problemas degenerativos ocasionados por uma possível metilação nos telomeros (12) , sendo a mitose totalmente dependente de ácido fólico; a presença deste é fortemente influenciada pela mutação na MTHFR (10,12,15,17) . O objetivo deste trabalho foi quantificar o número de indivíduos homozigotos para o alelo C e alelo T e heterozigotos.…”