Book chapter
DNA DAMAGE RESPONSE AND REPAIR: MECHANISMS IN AGING AND CANCER
DNA Damage Repair, Repair Mechanisms and Aging, pp.237-249
DNA Properties and Modifications Functions and Interactions Recombination and Applications, Nova Science Publishers, Inc
01/01/2010
Abstract
The preservation of expected life span and longevity as well as the assurance of life succession among all species requires the integrity and faithful transcription of DNA, which is in constant danger from both environmental and intracellular stressors, such as radiation or products of cellular metabolism, respectively. Thus, a dedicated machinery of DNA repair factors is responsible for reversing DNA damage across the genome. Efficient response to various effectors of DNA damage is also dependent on a complex network of sensors and mediators of stress signals which are upstream of DNA repair activation and together constitute components of the DNA damage response (DDR). The final outcome for the cell may vary according to the severity and persistence of the induced lesions, resulting in either precancerous phenotypes from mutagenic lesions, or in premature age-related pathologies in the context of enhanced apoptosis or senescence. In this article we review the contribution of functional deterioration of the DDR in the evolution of aging and carcinogenesis. We describe how defects in the tumor suppressor-, hormonal- and DNA repair-related processes result in aging acceleration and emergence of malignancy with inferences from the genotypes and phenotypes of clinically relevant progeroid and cancer syndromes and also based on data from mouse p53 knock-out and human gene polymorphism studies. From a reverse point of view, we discuss observations of age-related alterations in DDR. We also discuss the critical involvement of stem cells in the pathophysiology of aging and malignant conditions. Finally, we recapitulate current and future anti-aging, anti-cancer preventive strategies including diet and calorie-intake modification, exercise and pharmacologic interventions.
Details
- Title: Subtitle
- DNA DAMAGE RESPONSE AND REPAIR: MECHANISMS IN AGING AND CANCER
- Creators
- Panagiotis J. Vlachostergios - University of ThessalyIoannis A. Voutsadakis - University of Thessaly
- Contributors
- A E Thomas (Editor)
- Resource Type
- Book chapter
- Publication Details
- DNA Damage Repair, Repair Mechanisms and Aging, pp.237-249
- Publisher
- Nova Science Publishers, Inc; HAUPPAUGE
- Series
- DNA Properties and Modifications Functions and Interactions Recombination and Applications
- Number of pages
- 13
- Language
- English
- Date published
- 01/01/2010
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984806609302771
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