Telomeres, Senescence and Longevity: The Role of Oxidative Stress and Antioxidants

Gabriele   C.   Saretzki

Abstract

Considerable evidence shows that accumulation of oxidative damage to various cellular macromolecules may be causally associated with cellular senescence and different age-related degenerative diseases. Telomeres are nucleoprotein structures that protect the ends of linear chromosomes. Telomeres in human somatic cells shorten with each cell division. The amount of shortening is largely dependent on the amount of oxidative stress and genetically determined antioxidant properties. Intervention experiments have shown that lowering oxidative stress can reduce telomere shortening. That identifies telomeres as excellent biomarkers for oxidative stress and the antioxidant capacity of a cellular system or organism. The analysis of the mechanisms responsible for aging and longevity in different animal systems from nematodic worms to rodents have demonstrated a clear correlation between the capability of an organism to cope with oxidative stress and its life span. Caloric restriction experiments and the characterisation of the insulin metabolism enhanced our understanding of the aging process substantially. Powerful synthetic mimetics of antioxidant enzymes have been developed recently. Their use has been shown to decrease oxidative load in models for different degenerative diseases and seems encouraging for further pharmacologic intervention into aging and age-related diseases.

Keywords: insulin like growth factor, age-associated diseases, nucleoprotein, binding proteins, dna replication, human telomerase reverse

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