When time does not heal
DNA damage and age
Anna Kerman, XX2 century
As we age, our bodies inevitably become decrepit. Some changes, such as gray hair and wrinkles, are visible to the naked eye. Others, like high blood pressure, often go unnoticed – but can be deadly.
Our bodies may show signs of aging, but the same can be said about the genome. DNA is damaged as a result of certain chemical reactions, in addition, errors sometimes occur when copying it. Of course, there is some protection at the cellular level, but it is not perfect, so cells gradually accumulate damaged DNA during their lifetime.
As a result of these damages, the genome in different cells of the body differs somewhat. When cells divide, they pass on "mistakes" to their descendants, and the more "wrong DNA" accumulates, the higher the risk of consequences.
If these changes – we call them mutations – interfere with the control system of cell reproduction and survival, then cancer can occur. However, as the authors of a new study published in the journal Blood found out, the existing systems of protection against cancer in the body are somewhat more complex and reliable than previously thought.
Heredity plays a role in about 10% of cancer cases. Genes such as BRCA1 and TP53 are well known for their ability to increase vulnerability to cancer. And both of these genes are involved in coordinating the cell's response to DNA damage.
BRCA1 helps to repair specific DNA damage, in which both chains are "broken". The presence of a defective gene increases the risk of developing breast cancer and ovarian cancer. When DNA repair mechanisms break down, more and more mutations accumulate in cells, and cancer becomes almost inevitable.
In addition to genetics, the likelihood of developing cancer is influenced by a complex mixture of environmental factors and lifestyle factors.
When we study the genome of tumor cells, we can determine what exactly triggered the development of mutations. For example, lung cancer in smokers and non-smokers is characterized by different mutations, since compounds inhaled with smoke attack DNA in a specific way. Similarly, this method can be used to determine exactly which disorders in the mechanisms of DNA repair are present in the patient.
With smoking and burdened heredity, everything is more or less unambiguous. But even ordinary water can damage DNA – it interacts with methylated DNA. In general, damage to methylated DNA occurs so often that they are even considered as a molecular "clock" showing the aging process. But in some people, such damage accumulates much faster than usual.
For the new study, scientists selected three volunteers whose methylated DNA repair mechanisms were disrupted. All participants registered a defective form of the "repair" protein MBD4 and all developed an aggressive form of leukemia shortly after 30, usually found only in people over 60.
A drawing from an article in Blood – VM.
Methylation disorders play a role in the development of most oncological diseases, but in this case they have become the main driving force of the disease. It should be noted, however, that complete inactivation of MBD4 – as in the volunteers from the study – is rare, but even less pronounced violations of DNA repair mechanisms can significantly increase the risk of cancer, especially in the context of aging.
The study not only demonstrated that in some people the biological "clock" in cells goes "faster", but also pointed to the need to identify risk groups in the general population that need additional preventive examinations.
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