Title
DNA damage metabolism and aging
Author
Medisch Biologisch Laboratorium TNO
Mullaart, E.
Lohman, P.H.M.
Berends, F.
Vijg, J.
Publication year
1990
Abstract
As a result of permanent exposure to low levels of various endogenous and exogenous genotoxic agents, large numbers of lesions are continuously induced in the DNA of cells of living organisms. Such lesions could lead to dysfunction of cells and tissues, and they might well be the underlying cause of the age-related reduction of homeostatic capacity and the increased incidence of cancer and other diseases of old age. The rate of damage induction as well as the persistence of the lesions depends on the activity, efficiency and reliability of a wide variety of molecular defense systems. However, a certain degree of imperfection seems to be a general characteristic of most of these defense systems and this could lead to a gradual accumulation of DNA alterations during aging. Even when the original lesions are quickly removed, they can still lead to secondary changes in the DNA, such as DNA-sequence changes and changes in gene expression. This process would be accelerated in case of the occurrence of an age-related decline in the efficiency of these molecular defense systems. This review deals with the present knowledge on the occurrence of 'spontaneous' DNA damage in aging organisms, its potential sources, the influence of preventive and processive cellular defense mechanisms and its consequences in terms of DNA-sequence changes, DNA conformational and configurational changes and changes in gene expression. In general, it can be concluded from the data discussed here that, in spite of a number of discrepancies and conflicting results, an age-related accumulation of DNA alterations occurs at all levels, e.g., chemical structure, DNA-sequence organization and gene expression.
Subject
DNA lesions
Aging
Cell and tissue dysfunctioning
Diseases
DNA damage accumulation
DNA metabolism
Mutations
Age
Animal experiment
DNA damage
DNA repair
Gene expression
Human
Nonhuman
Priority journal
Review
Aging
Animal
DNA
Animalia
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TNO identifier
231302
ISSN
0921-8734
Source
Mutation Research - DNAging Genetic Instability and Aging, 237 (237), 189-210
Document type
article