Juvenon Health Journal volume 10 number 7 july 2011
By Benjamin V. Treadwell, Ph.D.
Getting older does have some advantages. Like becoming wiser, with more knowledge not only about our surroundings, but also about human behavior and motivations, including our own. Among the not-so-good senior experiences, there’s one that’s common, although less conspicuous than slowing down physically and mentally. That’s a decline in the quality of sleep.
In fact, research on sleep in the elderly has identified a much shorter period of deep, or non-rapid eye movement (non-REM) sleep. Shorter periods of non-REM sleep have been linked to depression and impaired memory and mental acuity. Only recently, however, have we begun to understand how/why this happens, biochemically speaking.
As a team from the University of Wisconsin Department of Psychiatry put it, “Sleep is perhaps the only major behavior still in search of a function.” This is somewhat surprising since sleep has been observed in all species studied to date, including insects.
Using the fruit fly (Drosophila), the Wisconsin group undertook a study to prove the theory that at least one of sleep’s functions is returning the synapses in the brain to normal size, which restores normal function. Let’s take a closer look at their experiments and results. They could have interesting implications for the aging human population.
Profile of a Synapse
One of the more complex structures of the nervous system, the synapse is responsible for carrying an electrical charge from one neuron to another. Where do these electrical charges come from?
During the course of a day, interacting with our environment activates neurons by initiating electrical-chemical currents. If an experience is especially intense (your boss gave you a raise or, on the negative side, you were in an accident), the corresponding current traveling along a neuron will be intense.
When the current reaches the junction between one neuron and another — the synapse — a fascinating response occurs. The structure changes shape, increasing in size in a plastic-like way. Hence the scientific term, synaptic plasticity.
The more you experience during the day, the larger your synapses become as your brain converts the events to long-term memory. Happily, this increase in the volume of synaptic fats, proteins and neurotransmitters does not cause your head to explode.
According to the “synaptic homeostasis hypothesis,” however, if the structures aren’t allowed to return to normal size, the result is mental confusion. In other words, intelligent brain function seems to depend on synaptic renormalization. Here’s where sleep comes in and, possibly, why the brain doesn’t function normally after an all-night party or an 18-hour plane trip.
Fruit Fly Findings
Now, back to the Wisconsin research team. They set out to directly prove that sleep is necessary for synaptic renormalization. They chose the fruit fly (Drosophila), commonly seen hovering around over-ripe bananas, for their experiments. Why this insect?
As already mentioned, previous studies have shown even insects need sleep. Drosophila has a central nervous system, including a brain and the important nerve circuit connectors, the synapses. And there is already extensive knowledge of the fruit fly’s structural and genetic features.
The investigators examined a specific area of the flies’ brains. They used a fluorescent probe and fluorescent microscopy, as well as additional biochemical techniques (too lengthy to describe here), for measurement.
First, the team focused on whether an increase in number and size of synapses actually did occur during waking hours. Flies examined after seven hours of being awake in a normal environment had significantly more synaptic structures than those examined after seven hours of sleep.
Next, the researchers housed a group of flies in an environment that kept them more socially active during their waking hours. Synaptic activation and growth was even greater in this group.
In a third trial, flies were housed in a rotating cage, which prevented them from sleeping at all. Not only were this group’s synaptic membranes bloated, but these insects also demonstrated disoriented behavior.
So, keeping the fruit fly’s brain awake produced the anticipated results. Greater and/or longer stimulation, i.e., an enriched environment or total sleep deprivation, amplified the synaptic effects.
Renormalizing with Sleep
Next question? Is sleep necessary to “renormalize” the synapses (or bring them back to normal size)? The third group of flies demonstrated the opposite effect. With prolonged sleep deprivation, their synaptic membranes remained bloated, corresponding to abnormal behavior and impaired learning.
On the other hand, flies from the first two groups were allowed to sleep. They woke up exhibiting typical behavior and learning ability. Their synapses had also trimmed to normal (pre-waking hour) size. Or to put it another way for the fruit fly, at least, sleep is required to renormalize the size/strength of the synapse. Effective brain function is dependent on this synaptic homeostasis or renormalization.
In Human Terms
The work with Drosophila suggests sleep may be essential to helping humans stay mentally sharp. It provides insight into how sleep resets our nervous system to function optimally. There are some indications sleep may also be necessary to return the synapse at the neuromuscular junction to normal size after exercise.
Understanding sleep’s function physiologically may be a first step toward learning why the quality of human sleep seems to decline with age. (See Juvenon Health Journal Volume 7, Number 1, “Stages of Sleep: Could the Last be the Best for Whole Body Health?”) Being aware of the importance of the behavior, in itself, may actually help improve its quality. Perhaps it will encourage us to live a lifestyle (exercise, moderate alcohol intake, a healthy diet and attitude) that promotes longer deep sleep.
answers your questions.
question: I’ve been having trouble sleeping through the night, giving me time to play a lot of solitaire and do some research. I’ve learned this is not uncommon at my age (60-plus), along with the poor memory and thought processes lack of sleep may cause. I’ve also read that more restful sleep may be one of the benefits of taking Juvenon. Your opinion and/or explanation? thanks. — S
answer: Although I’ve received several letters attributing better sleep to taking Juvenon, so far, the evidence is anecdotal. A clinical study may be on the horizon. For now, here are two possible explanations for this phenomenon.
One of the Mayo Clinic’s tips for achieving better sleep is to include physical activity in your daily routine. Experiments have shown that Juvenon’s formula helps maintain and improve the function and number of mitochondria in the body, consequently producing more energy. People with more energy tend to be more active.
A more efficient mitochondrion also produces fewer oxidants and provides the energy to clean cellular house, so to speak. The cell becomes more effective at maintaining biochemical balance. Restoring the sleep center cells in the brain to this homeostasis could, in theory, improve their function and your rest.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.
A recent Science magazine article, “Sleep and Synaptic Homeostasis: Structural Evidence in Drosophila,” summarizes some interesting findings on sleep’s function. Investigators, from the University of Wisconsin’s Department of Psychiatry, examined sleep’s effect on the connections between neurons in the brain, the synapses. They wanted to directly prove that sleep is necessary for synaptic renormalization (return to normal size) and, consequently, normal brain function.
The research team was aware of published reports showing that all animals, studied to date, require sleep. To test for the need for synaptic renormalization, also known as the “synaptic homeostasis hypothesis,” they selected the common fruit fly (Drosophila). The fruit fly is not only well understood both genetically and structurally, but also has a brain with known structural components in specific areas.
Using a variety of investigative tools, including fluorescent-labeled probes that bind to specific areas on synaptic membranes, the researchers demonstrated that the fly’s synapses increase in size during its waking hours. As expected, after a period of sleep, the synaptic membranes return to normal size.
In another experiment, the team added flies to the cage to increase the fruit flies’ social interaction. This mental stimulation produced a significant increase in the size of the synaptic membrane, as compared to flies kept in a more normal environment.
The researchers used a special rotating cage to prevent subject flies from sleeping for a third trial. They observed abnormal fly behavior. The animals were disoriented with diminished learning capacity. As predicted, their synaptic membranes were bloated.
The team concluded that keeping the brain awake, at least in the fruit fly, increases synaptic size/strength. Because stronger, larger synapses require more energy and space, this condition becomes unsustainable. The brain cannot effectively record and process information any longer. Sleep serves an essential function by promoting a reduction in synaptic strength and size to sustainable levels.
These findings are particularly interesting, not only because of how they may translate to humans. The research also provides more insight into sleep, itself, a behavior science is only beginning to understand.
Read abstract here.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.