Sleep deprivation is linked to numerous deleterious conditions, including reduced cognitive ability and immune system effects.
Some evidence suggests that DNA damage can be another deleterious effect of bad sleep patterns, particularly among those who do shift-work or work uncomfortable hours. The effects of DNA damage can lead to the development and progression of chronic diseases.
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When does sleep deprivation cause DNA damage?
The exact method through which disruption to sleep can cause DNA damage is not entirely known, as it appears this can happen through several systems. These include changes to the expression of certain genes, particularly those associated with aging and DNA repair, and oxidative stress.
Sleep deprivation can affect genes associated with both DNA repair and DNA damage. A study comparing doctors who worked day or night shifts found that those working the night shift had 30% lower baseline levels of DNA repair gene expression and more DNA breaks than those who did not work night shifts. After acute sleep deprivation, both these indicators of DNA damage were further exacerbated by 25%.
In addition to night shift work contributing to DNA damage, there is some evidence that this can occur in a dose-dependent manner. When 2 million participants were pooled for a meta-analysis, results showed that more night shift work led to an increased risk of breast tumors.
However, temporal studies on other cancers have had mixed results. It is believed that the development of chronic diseases like these is due to DNA damage.
There is also some evidence that sleep deprivation does not need to be acute to cause DNA damage.
A study on older adults, which tested only one night of partial sleep deprivation, found that this led to increased expression of senescence-associated secretory phenotype and leukocytes indicative of DNA damage responses. This links poor sleep with processes associated with aging, in addition to more general DNA damage.
Genes and mechanisms of DNA damage
The genes involved in DNA repair that appear to be affected by sleep deprivation include ERCC1, OGG1, and XRCC1 genes. These are involved in nucleotide excision repair, base excision repair, and recombinational repair.
Decreased levels of these genes, and therefore decreased occurrence of their associated functions, are linked to the accumulation of DNA damage, higher mutation rates, and tumorigenesis.
While the exact reason for sleep is largely still debated, its underlying commonality is that it seems to be essential for the functioning and health of the nervous system.
Studies in zebrafish show that sleep is directly linked to neuronal physiology, but that changes occurring in neurons during sleep do not occur in cell types that are not excitable.
The changes occurring in neurons during sleep relate to the mending of DNA damage. During wakefulness, breaks in double-stranded DNA increase, and chromosome dynamics are low.
Furthermore, a neuronal activity that contributes to DNA damage can further reduce chromosome dynamics. During sleep, chromosome dynamics increase which allows for the mending of the DNA double-strand breaks.
There is also some evidence that the relationship between chromosome dynamics and breaks in the DNA requires a threshold of DNA damage. In yeast, chromosome mobility increases once a threshold of DNA damage is reached, and continuous wakefulness in fish inhibits chromosome dynamics.
This indicates that sleep is triggered after a threshold of DNA damage is reached, to allow for a balanced relationship between DNA damage and DNA repair.
Current limitations and future directions
One of the major limitations to our current understanding of how sleep deprivation can induce DNA damage is the lack of subjects experiencing sleep deprivation. Most studies are carried out on older populations, so the findings of these studies may not always apply to younger populations who are less likely to suffer from sleep deprivation.
Similarly, many night shift workers are younger, and therefore generally more robust to disruptions in sleep patterns, which can make it difficult to find an adequate control group in the same age range.
The role of shift workers and others who experience sleep deprivation through slightly altered life paces are often indirect studies. For example, one study found that people who work overnight can have DNA damage relies on the presence of 8-hydroxydeoxyguanosine concentrations in the urine, which functions as an indirect measure of DNA damage and DNA repair levels.
There are also a lot of gaps in the knowledge of how sleep contributes to fighting DNA damage. For example, while there is evidence that chromosome dynamics increase during sleep, the reason for this is not known.
It is proposed to be linked to increased efficiency in reducing double-strand breaks in DNA or to aiding in the regulation of gene expression levels, which generally peak during wakefulness and are reduced during sleep.
Sources
- Cheung, V. et al. (2019). The effect of sleep deprivation and disruption on DNA damage and health of doctors. Anesthesia. https://doi.org/10.1111/anae.14533
- Zada, D. et al. (2019). Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons. Nature Communications. https://doi.org/10.1038/s41467-019-08806-w
- Carrol, J.E. et al. (2016). Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adults humans. Brain, Behavior, and Immunity. https://doi.org/10.1016/j.bbi.2015.08.024
Further Reading