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Chromosomal Damage and Ageing
Posted on: October 19, 2005

The ageing process consists of structural alterations and functional declines in body systems with a consequent impairment of homeostasis with increased vulnerability to age-related diseases, ultimately leading to death. The effects of ageing in individuals appear to be a combination of genetically programmed processes and genetic alterations induced by exogenous and endogenous factors. The increase of cellular components, damaged by highly reactive free radicals and associated with decreased DNA repair capability, play a central role in genetic instability, a common marker of cancer and age-associated degenerative diseases.

There is an age-related increase in DNA damage and in the mutation rate and variations in different genetic end-points – such as DNA adducts, DNA breaks or alkali-labile sites, mutations at different genetic loci and chromosomal damage. The presence of chromosomal abnormalities was the first genetic change to be specifically associated with age. An increase in basal levels of chromosomal damage dependent on age has been detected for sister chromatid exchange, chromosomal aberrations and micronuclei (MN) frequency. Age affects sister chromatid exchange, although the increase in old age is limited (~10-15%).

The effect of age on chromosomal aberration frequency is unclear. Recently biomonitoring studies showed that stable cytogenetic changes accumulate with age.

The increase in spontaneous chromosomal instability with age, as reflected in the higher basal level of MN frequency, is associated with an accumulation of DNA damage due to a progressive impairment of overall DNA repair capacity. A similar pattern of chromosomal instability occurs in different premature ageing syndromes characterized by defective DNA damage defense mechanisms.

Figure 1. Frequency of standardized micronuclei (sMN) by age group and sex.
Black columns are female data; white - male; n.s - not significant.

Changes in chromosomal structure or function are strongly associated with ageing, although scientific results cannot determine whether these changes are part of the cause or a consequence of ageing.

Key points

  • Ageing is associated with changes in chromosomal structure and function.
  • Spontaneous micronuclei frequency in peripheral blood lymphocytes is a measure of chromosomal damage.
  • There is an age-related increase of spontaneous micronuclei frequency in peripheral blood lymphocytes.
  • Scientific studies confirm the role of age as a confounding factor on baseline frequency of micronuclei. This parameter has to be considered in the study design and analysis of biomonitoring studies aimed at evaluating exposure to genotoxic agents.
Source: Bolognesi C., Lando C., Forni A., Landini E., Scarpato R., Migliore L., Bonassi S. Age and Ageing 1999; 28:393-397.
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