Study shows new evidence of age-related decline in the brain's master circadian clock
(Medical Xpress) -- A new study of the brain's master circadian clock known as the suprachiasmatic nucleus, or SCN reveals that a key pattern of rhythmic neural activity begins to decline by middle age. The study, whose senior author is UCLA Chancellor Gene Block, may have implications for the large number of older people who have difficulty sleeping and adjusting to time changes.
"Aging has a profound effect on circadian timing," said Block, a professor of psychiatry and biobehavioral sciences and of physiological science. "It is very clear that animals' circadian systems begin to deteriorate as they age, and humans have enormous problems with the quality of their sleep as they age, difficulty adjusting to time-zone changes and difficulty performing shift-work, as well as less alertness when awake. There is a real change in the sleepwake cycle.
"The question is, what changes in the nervous system underlie all of that? This paper suggests a primary cause of at least some of these changes is a reduction in the amplitude of the rhythmic signals from the SCN."
The SCN, located in the hypothalamus, is the central circadian clock in humans and other mammals and controls not only the timing of the sleepwake cycle but also many other rhythmic and non-rhythmic processes in the body.
This video is not supported by your browser at this time.The UCLA research team examined the SCN in mice and found that while critical neural activity rhythms were already disrupted in middle age, the molecular mechanisms that generate these rhythms were not significantly altered.
"These results indicate that the outputs of the central circadian clock start to decline in middle age and suggest that the same may be true in humans," said study co-author Christopher Colwell, a UCLA professor of psychiatry and biobehavioral sciences who has conducted research with Block for many years. "Before this study, we did not know that the SCN was the site where the decline occurs."
In a technical tour de force, the research team successfully recorded electrical activity from the brain's SCN not in a Petri dish but in living animals. The research marks the first time this has been achieved in middle-aged animals and the first time scientists have watched the central biological clock of aging animals in action. The study was published July 13 in the Journal of Neuroscience, the journal of the Society for Neuroscience.
The scientists studied young mice, which were just a few months old, and middle-aged mice, which were more than a year old. SCN brain cells are electrically active during the day and electrically silent during the night in younger animals and younger people, the researchers said, but that difference is reduced with aging.
"The changes we observed in the electrical rhythm between the young and middle-aged animals, which are quite dramatic, occur even though we do not see significant changes in the underlying molecular rhythm," Block said. "Our hypothesis is that the age-related changes in the circadian timing system are primarily occurring, at least initially, at the level of the electrical output signaling, perhaps mediated by changes in the cell-membrane properties of SCN clock cells. This is good news, because it points where in the cell to look for the age-related 'lesion' and thus helps inform what type of measures may be available to reduce these age-related deficits."
Block and Colwell suspect the process is similar in humans.
The SCN keeps the system of multiple distributed circadian oscillators in synchrony, but disruptions in the SCN lead to disrupted sleep, as well as dysfunction in memory, the cardiovascular system, and the body's immune response and metabolism.
The SCN, Block said, can be imagined as a heavy pendulum that controls many light pendulums (oscillators), with rubber bands between them.
"If the central clock weakens, it's effectively like making those rubber bands thinner and weaker," Block said. "When the SCN ages and those rubber bands become weaker, it becomes hard for the SCN to synchronize all of these other oscillators."
In the young mice, the scientists found high levels of activity during the day and much lower activity levels during the night. In middle-aged mice, there was not nearly as large a difference in activity between the day and the night.
"In the middle-aged mice, they still have a circadian rhythm, but the amplitude is reduced," Block said. "During the nighttime, when electrical impulse activity levels are usually fairly low, the levels have increased. Thus, the difference between the highest levels of activity during the daytime and the lowest levels of activity during the nighttime is much smaller in the middle-aged mice."
Large numbers of people over the age of 65 regularly take sleeping pills, but the effects of taking such pills over many years is not known, said Colwell, who hopes the new research will lead to other options for getting a good night's sleep.
Colwell, Block and their team plan to pursue follow-up research on treatment options that could enhance the function of the circadian system with aging. They are studying the specific membrane channel changes in the SCN that are responsible for the electrical rhythm and also are looking at the circadian regulation of the heart and the mechanisms underlying neural activity rhythms in the SCN.
Their research could potentially lead to new ways of boosting the circadian output. It is possible, Colwell and Block said, that relatively simple approaches could be beneficial, such as exercising early in the morning, getting regular exposure to bright light, eating meals at consistent times and, when traveling, eating meals at the appropriate local time, regardless of whether one is hungry then.
Possible interventions may involve discovering ways to improve the sleep cycle of aging people and their ability to better handle time-zone changes, perhaps by boosting the amplitude of the SCN. New pharmaceutical approaches may be developed, the scientists said. Future research may reveal which approaches are likely to be most effective.
Co-authors of the study included lead scientist Takahiro Nakamura, a former UCLA postdoctoral scholar in Colwell and Block's laboratory, who is currently on the faculty of Japan's Teikyo Heisei University; Takashi Kudo, a UCLA postdoctoral scholar; and Tamara Cutler, a UCLA undergraduate student who works in Colwell and Block's lab.
Implications for patients with neurological disorders such as Parkinson's
In related research, Colwell and his colleagues have documented that changes similar to those that occur as we age also occur in mouse models of neurodegenerative disorders like Huntington's disease and Parkinson's disease.
"With many neurological disorders, patients have a hard time sleeping during the night and staying awake during the day," said Colwell, who was a postdoctoral fellow in Block's lab in the early 1990s at the University of Virginia. "One of the main clinical complaints of patients with Huntington's disease and Parkinson's disease is they cannot sleep and do not respond well to sleeping pills. We think the same dysfunction we see with normal aging occurs much earlier and more severely with these patients, and we hope that the treatment strategies we develop for aging can be applied to help patients with neurodegenerative diseases as well. If we learn what is going wrong, then we may be able to develop treatments."
Colwell's research on Huntington's disease was published earlier this year in the journal Experimental Neurology, and his research on Parkinson's has been accepted for publication in the same journal.
Provided by University of California Los Angeles
- Separating morning and evening in the circadian clock of mammals Jun 24, 2005 | not rated yet | 0
- Study reveals little-known cell networks vital to circadian rhythm May 03, 2007 | not rated yet | 0
- Protein shown to rally biological clock Nov 29, 2006 | not rated yet | 0
- Temperature rhythms keep body clocks in sync, researchers find Oct 14, 2010 | not rated yet | 0
- Mouse vision has a rhythm all its own Aug 23, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
15 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Trends in Helicobacter pylori (H. pylori) and smoking explain a significant proportion of the decline of intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence in US men between 1978 and 2008, and are estimated ...
Medical research 4 hours ago | not rated yet | 0
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 9 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 10 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 10 hours ago | 4.8 / 5 (4) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 13 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
10 hours ago | 4 / 5 (4) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
8 hours ago | 4.8 / 5 (6) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
4 hours ago | 5 / 5 (1) | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
4 hours ago | 5 / 5 (3) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
5 hours ago | not rated yet | 0 |
Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer's Disease in mice.
7 hours ago | 5 / 5 (3) | 0 |