Oxidative Telomere Attrition, Nutritional Antioxidants and Biological Aging - Oxidative Telomere Attrition, Nutritional Antioxidants and Biological Aging - Open Access Pub

Telomeres are strings of DNA that are not themselves genes but that extend every chromosome beyond its last gene. Terminal telomeres are sacrificed during every mitotic event in human cells (“telomere attrition”), preserving the functional genome despite the “end replication problem.” However, the “telomeric theory of biological aging” suggests that when an individual cell has reproduced itself a sufficient number of times (the “Hayflick limit”), some the its telomeres have become critically shortened (“telomeric crisis”) and cannot completely “cap off” a chromosome, and any further attempts to replicate such a chromosome would produce damaged DNA and a dysfunctional cell (“cellular aging”). As cells enter telomeric crisis, they usually initiate intracellular signaling cascades that arrest DNA replication and mitotic activity, converting biologically active cells into inactive cells (“cellular senescence”). The progressive accumulation of senescent cells impairs the healthy functioning of tissues and produces “biological aging.” Oxidative stress damages telomeres and accelerates telomere attrition and biological aging. Premature biological aging is associated with degenerative diseases and diminished quality of life. Reducing the level of systemic oxidative stress can ease the oxidative drive toward cellular senescence and premature biological aging. Increased intakes of antioxidant-rich foods and specific antioxidant nutrients (such as fruits and vegetables, α -lipoic acid, astaxanthin, eicosapentaenoic acid, docosahexaenoic acid, trans-resveratrol, N-acetylcysteine, methylsulfonylmethane, lutein, vitamin C, vitamin D, vitamin E, and γ-tocotrienol) may decrease cellular and systemic oxidative stress and decelerate biological aging. DOI10.14302/issn.2379-7835.ijn-14-606 Telomeres, Senescence and Biological Aging Human telomeres are strings of nucleotides located on the tips of chromosomes that repeat the “nonsense” sequence, TTAGGG, thousands of times.1 Instead of providing genetic information, telomeres protect chromosomal integrity. The last telomeres on the 3’ end of a chromosome combine with a set of proteins (the shelterin complex) to form loop-like structures that prevent 1) the “loose” ends of chromosomal DNA strings from being mistakenly identified by the DNA repair machinery as broken DNA strands that require repairing, and 2) subsequent well-intentioned but misguided repair attempts that could produce harmful mutations.1,2,3,4,5,6 When a cell is replicating its DNA prior to undergoing mitosis, the DNA polymerase-containing replication complex