Nucleotide-excision repair deficiency: Acausative factor for accelerated aging diseases in humans?
Nucleotide excision repair (NER) recognizes and removes bulky DNA damage that leads to DNA double-helix distortion. Inherited defects in the NER pathway have been associated with aging symptoms and premature death. In this review, we discussed the mechanisms of how NER maintains genomic integrity and affects clinical outcomes, if NER is compromised, and the role of NER as a potential causative factor for mammalian aging. We summarized current evidence of the association between NER and aging process through a discussion of most updated research findings from genetic models of mice and molecular epidemiological studies from humans. Several possible mechanisms by which NER influences aging are suggested, including the GH/IGF1 axis, p53-induced apoptosis/senescence in response to DNA damage, reactive oxygen species (ROS), and maintenance of telomerase activities. A comparison between normal aging and NER deficiency-related aging is also made to illustrate their similarities and discrepancies. We conclude with a number of issues needed to be resolved to further clarify the relationship between NER and aging process in humans. © 2010 Nova Science Publishers, Inc. All rights reserved.
