DNA repair-deficiency disorder

An DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.

Examples

Some of the examples include:

• Ataxia telangiectasia
  
• Bloom syndrome
• Cockayne's syndrome
• 
  
• Progeria (Hutchinson-Gilford Progeria syndrome)
• Rothmund-Thomson syndrome
  
• Trichothiodystrophy
• Werner syndrome
• Xeroderma pigmentosum

DNA repair defects distinguished from "accelerated aging"

Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (usually some of both). But elimination of any gene essential for base excision repair kills the embryo -- it is too lethal to display symptoms (much less symptoms of cancer or "accelerated aging"). Rothmund-Thomson syndrome and xeroderma pigmentosum display symptoms dominated by vulnerability to cancer, whereas progeria and Werner syndrome show the most features of "accelerated aging". Hereditary nonpolyposis colorectal cancer (HNPCC) is very often caused by a defective MSH2 gene leading to defective mismatch repair, but displays no symptoms of "accelerated aging". Some DNA repair defects manifest as neurodegeneration rather than as cancer or "accelerated aging".

Debate concerning "accelerated aging"

Some biogerontologists question that such a thing as "accelerated aging" actually exists, at least partly on the grounds that all of the so-called accelerated aging diseases are segmental progerias. Many disease conditions such as diabetes, high blood pressure, etc. are associated with increased mortality. Without reliable biomarkers of aging it is hard to justify the claim that a disease condition represents more than accelerated mortality.

Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage. The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging". Such conditions, it is argued, are readily distinguishable from genetic diseases associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis and sickle cell anemia. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases such as cancer and Alzheimer's disease.