Whether you’re a morning person or a night owl, your body clock plays a vital role in determining your level of cognitive performance at different times of the day. While these cycles can be influenced by lifestyle tendencies, they are largely controlled by genetic factors, as different genes tend to become expressed at certain times of the day and night.
However, researchers have recently discovered that this rhythmic expression becomes disrupted as we age, possibly contributing to the development of a range of degenerative mental disorders, such as Alzheimer’s disease. And by observing the ways in which the body naturally attempts to correct the faltering synchronicity of its own internal clock, scientists may be able to develop novel treatments for some conditions associated with age-related deterioration.
It has long been known that physiological processes tend to occur in daily cycles, known as circadian rhythms. In a 2013 study, researchers observed the brains of 55 deceased people whose time of death was known. By studying which proteins were being synthesized in these brains as they perished, the team was able to discern which genes were being expressed at that exact moment, and used this to accurately predict the time of day when each individual had died. From this, they were able to identify a wide number of genes that follow a rhythmic daily cycle, and therefore help to ‘set’ the circadian clock.
Building on these results, a separate group of researchers has now published a study in the Proceedings of the National Academy of Sciences, looking at 146 well-preserved human brains. Using a process called microarray analysis, the team were able to determine which proteins were being processed at the time of death, from which they then identified a core set of 235 genes with significant circadian rhythms of expression.
Since all brains examined were either younger than 40 or older than 60 at the time of death, the researchers were able to search for age-dependent patterns in these circadian rhythms. They discovered that many genes lost their rhythmicity in older individuals, which may explain a number of behavioral traits that are commonly associated with aging. For instance, a condition known as sundowning affects many dementia sufferers, whereby they tend to display a higher cognitive function in the morning but become increasingly delirious, agitated and confused in the evening.
Many dementia sufferers are more lucid in the morning than the evening – a condition known as sundowning. Monkey Business Images/Shutterstock
Interestingly, however, they found that a number of other genes actually gained rhythmicity in older individuals. In total, the team found more than 1,000 genes that displayed age-related alterations in rhythmicity, and hypothesize that the increased rhythmicity of certain genes may represent a natural attempt to compensate for the deterioration of the circadian clock, essentially creating a new one to replace the old rhythmicity. For instance, certain genes associated with the regulation of beta-amyloid proteins – which contribute to the development of Alzheimer’s – are among those that tend to gain rhythmicity in old age, thereby providing a level of protection against the condition.
Variations in this acquired rhythmicity between individuals may therefore partially explain why some people suffer from degenerative disorders like dementia while others do not. As such, the study authors propose that by increasing our understanding of how these cycles of rhythmic gene expression are controlled, it may be possible to develop new treatments for certain age-related conditions in the future.
