The circadian rhythm of gene activity changes with aging, and a novel biological clock begins ticking only in the older brain, says a study published in Proceedings of the National Academy of Sciences.
A 24-hour circadian rhythm controls the majority of brain and body processes, such as the sleep/wake cycle, metabolism, alertness and cognition. These daily activity patterns are regulated by certain genes that are found in most cells but have rarely been studied in the human brain.
Previous studies have reported that older adults tend to perform complex cognitive tasks better in the morning and progressively worse through the day. The circadian rhythm is also known to change with aging, leading to awakening earlier in the morning, fewer hours of sleep and less robust body temperature rhythms.
Senior co-investigator Etienne Sibille, PhD – formerly a professor of psychiatry at the University of Pittsburgh School of Medicine in Pennsylvania, and now the Campbell Family Chair in Clinical Neuroscience at the Centre for Addiction and Mental Health at the University of Toronto – had also previously shown that gene changes or “molecular aging” occurs in the brain.
Researchers at the University of Pittsburgh School of Medicine looked at the effects of normal aging on molecular rhythms in the human prefrontal cortex, an area of the brain involved in learning, memory and other aspects of cognitive performance.
They studied thousands of genes from brain samples of 146 people with no history of mental health or neurological problems. Families of the individuals had donated their remains for medical research, and the time of death was known.
The researchers categorized the brains depending on whether they had come from a person younger than 40 or older than 60. They then used a newly developed statistical technique to analyze two tissue samples from the prefrontal cortex for rhythmic activity, or expression, of thousands of genes.
Using information about the time of death, they identified 235 core genes that make up the molecular clock in this part of the brain.
They found that younger people had the daily rhythm in all the classic “clock” genes. Older people appeared to have lost rhythm in many of these genes, but they also had a set of genes that gained rhythmicity.
Senior investigator Colleen McClung, PhD, believes this could explain some of the changes that older people experience in sleep, cognition and mood.
The findings could lead to the development of treatments for cognitive and sleep problems that can occur with aging, and also for “sundowning,” a condition in which older individuals with dementia become agitated, confused and anxious in the evening.
“Since depression is associated with accelerated molecular aging, and with disruptions in daily routines, these results also may shed light on molecular changes occurring in adults with depression.”
Next, the researchers hope to explore the function of the brain’s circadian-rhythm genes in lab and animal models. They also hope to find out whether the rhythms are altered in people with psychiatric or neurological illnesses.
Medical News Today reported earlier this year on the discovery of a “body clock switch,” believed to affect people’s circadian rhythms.