Ageing and DNA damage

DNA damage can accelerate ageing
Single strand (top) and double strand (bottom) DNA breaks. Image from Wiki Commons

This post is part of a series on What Causes Ageing.

DNA inside our cells is constantly being damaged by products of metabolism such as reactive oxygen species and environmental factors like UV light, radiation, and smoking. DNA damage changes the basic chemical structure of DNA. This happens between 10 000 and 1 000 000 times a day in every cell in our body. So our cells have several inbuilt mechanisms to repair DNA. Despite these repair mechanisms, DNA damage can accumulate over time. So old cells have more DNA damage than young cells.

The question is ‘Does DNA damage cause ageing, or does ageing cause more DNA damage?’ It seems to be a little of both. DNA damage can cause cells to function less efficiently. If they are really damaged, they will die. Distressed or dying cells can send out signals that damage surrounding cells. If this happens enough, whole tissues or organs will stop working properly. This is one proposed mechanism of ageing. The converse is also true. As cells age, they can accumulate DNA damage – particularly cells in an organ that doesn’t regenerate much like the brain or the heart – and so are more likely to develop mutations.

This can become a vicious cycle if mutations occur in DNA repair genes. If a cell has defective DNA repair or accumulates a lot of DNA damage, particularly in genes essential to the cell’s normal function, it will be programmed to die by apoptosis, become senescent and unable to divide, or in the worse case scenario will divide uncontrollably and cause cancer.

Sometimes mutations in DNA repair genes are inherited. People with these inherited mutations often age very quickly. This is the cause of diseases like Werner Syndrome and Cockayne Syndrome. The fact that DNA repair mutations can cause accelerated ageing supports the hypothesis that DNA damage contributes to ageing.

The Scientific Papers

John Carroll and Petros Marangos. The DNA damage response in mammalian oocytes. Frontiers in genetics. 2013.

Carol Bernstein et al. DNA Damage, DNA Repair and Cancer – Chapter 16 of New Research Directions in DNA Repair. 2013.

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