Nucleotide excision repair deficiencies and the somatotropic axis in aging.
The physicochemical constitution of DNA cannot warrant lifelong stability. Yet, unlike all other macromolecules, nuclear DNA must last the lifetime of a cell ensuring that its vital genetic information is preserved and faithfully transmitted to progeny. An increasing body of evidence suggests that progressive genome instability likely contributes to aging and shortens lifespan. In support, defects in genome surveillance pathways rapidly accelerate the onset of age-related pathology, including cancer. This review describes the role of DNA damage in aging along with a number of progeroid syndromes and associated mouse models with defects in nucleotide excision repair that age rapidly and die prematurely.
Garinis
George A
GA
Department of Genetics, Erasmus Medical Center, Rotterdam, the Netherlands. g.garinis@erasmusmc.nl
D000375:Aging / Q000502:physiology*; D000818:Animals; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair / Q000502:physiology*; D004195:Disease Models, Animal; D019382:Human Growth Hormone / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology; D051379:Mice
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D004247:DNA