Clock genes change with age
As we age, some genes that obey the circadian rhythms are replaced by others
Kirill Stasevich, "Science and Life", based on the materials of The Scientist: An Aging-Related Effect on the Circadian Clock
There is no need to remind you again how much in a living organism depends on the circadian rhythms: this is not only the alternation of sleep and wakefulness, but also the features of memory formation, the restructuring of neural circuits, immunity, metabolism, etc. And sleep, and immunity, and everything is controlled by a huge number of genes, and rhythmic changes are due to the fact that at different times of the day many of them work differently, their activity increases and decreases.
If there are any problems in the rhythms, if the genes, for example, begin to activate at the wrong time, or their rhythmic activity disappears altogether, then the body begins to have serious problems. For example, it is known that neurodegenerative processes develop due to damaged "clocks", intracellular stress increases, problems with metabolism begin. The same thing, by the way, happens with age, so it was assumed that age-related diseases occur, among other things, due to breakdowns in the regulation of circadian rhythms.
The biological clock does change over the course of life, but it's probably not only and not so much in the general attenuation, "straightening" of rhythms. Researchers from the University of Oregon decided to compare how the clock changes with age in fruit flies.
It is known that the activity of a gene can be determined by the amount of matrix RNA (mRNA) that is synthesized on this gene. Matrix RNA serves, roughly speaking, as an intermediary between DNA and molecular machines that assemble proteins. In general, if we ignore some details, we can say that the more mRNA is synthesized, the more protein is obtained and the stronger the cell feels the work of the gene. The synthesis of RNA, in turn, is subject to various regulators, among which there is a mechanism of circadian rhythms. And if we analyze how the level of matrix RNA from a particular gene changes during the day, we will find out whether the gene depends on circadian rhythms or not.
That's exactly what David A Hendrix and his colleagues did: they compared RNAs synthesized on different genes of fruit flies when they were five days and fifty-five days old. (One day of the drosophila's life can be equated to one year of human life, so you can imagine what the age difference was between these experimental flies.) Both those and others had genes that obeyed the daily schedule, but with age, in many genes, the daily changes in activity disappeared, and only 45% remained "rhythmically active" in older flies. It would seem that there is an age-related shutdown of the biological clock. However, as the authors of the work in Nature Communications (Kuintzle et al., Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging), other genes that had not previously responded to the instructions of the internal clock suddenly became rhythmic in older flies.
A drawing from an article in Nature Communications – VM.
Many of the "late rhythmic" genes were anti-stress. They worked not only in old fruit flies, but also in young ones – for this, the insects needed to arrange oxidative stress by placing them in an environment with a high oxygen content. Interestingly, the anti–stress genes, when they were turned on in young flies, began to work in a circadian rhythm - that is, the same way they worked in old flies. And if the clock gene was turned off in drosophila, which is considered the main "clockmaker" and on which the rhythmic activity of other genes depends, then in young insects the anti-stress genes stopped working on a daily cycle.
Several important conclusions follow from the results obtained. Firstly, as we have already said, it cannot be argued that with age the biological clock simply breaks down – the fact that some genes eventually cease to be "active" in the circadian rhythm means that others take their place in the biological clock. Secondly, as it turned out, some anti-stress genes work in a rhythmic mode, regardless of the age at which their owner is. In youth, the body is able to cope with the same oxidative stress without additional effort, and it is necessary to include the corresponding genes only in extreme cases, but if this happens, they will work again "by the clock".
It is not yet clear how the effectiveness of anti-stress mechanisms will change if they are deprived of a daily "schedule"; it is very likely that they need just such a temporary organization for effective functioning, and that in the absence of a "schedule", antioxidant genes will stop fighting oxidative stress properly. Whether it is true or not, the researchers are going to find out soon.
Recall that some time ago we wrote about a similar work – in 2015, an article was published in the journal PNAS, which stated that some of the clock genes of the human brain lose the ability to monitor the circadian rhythm over time, but others, on the contrary, become new "details" of the biological clock with age.
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27.02.2017