One of the hallmarks of Alzheimer’s disease is disruption to the body’s circadian rhythm, the internal biological clock that regulates many of our physiological processes. Nearly 80% of people with Alzheimer’s experience these issues, including difficulty sleeping and worsening cognitive function at night. However, there are no existing treatments for Alzheimer’s that target this aspect of the disease.
A new study from researchers at University of California San Diego School of Medicine has shown in mice that it is possible to correct the circadian disruptions seen in Alzheimer’s disease with time-restricted feeding, a type of intermittent fasting focused on limiting the daily eating window without limiting the amount of food consumed.
“Circadian disruptions in Alzheimer’s are the leading cause of nursing home placement,” said Desplats. “Anything we can do to help patients restore their circadian rhythm will make a huge difference in how we manage Alzheimer’s in the clinic and how caregivers help patients manage the disease at home.”
Compared to control mice who were provided food at all hours, mice fed on the time-restricted schedule had better memory, were less hyperactive at night, followed a more regular sleep schedule and experienced fewer disruptions during sleep. The test mice also performed better on cognitive assessments than control mice, demonstrating that the time-restricted feeding schedule was able to help mitigate the behavioral symptoms of Alzheimer’s disease.
The researchers also observed improvements in the mice on a molecular level. In mice fed on a restricted schedule, the researchers found that multiple genes associated with Alzheimer’s and neuroinflammation were expressed differently. They also found that the feeding schedule helped reduce the amount of amyloid protein that accumulated in the brain. Amyloid deposits are one of the most well-known features of Alzheimer’s disease.
Melatonin and its derivatives found to enhance long-term object recognition memory
Multiple studies have demonstrated the memory-enhancing effects of melatonin and its derivatives in animal models. It is also known that the formation of both short- and long-term memories require the phosphorylation of certain memory-related proteins.
However, the molecular mechanisms underlying melatonin-induced memory enhancement have remained elusive. Now, medical researchers from Sophia University, Japan, have made important findings that contribute significantly to the elucidation of the underlying mechanisms in a recent article that was published NeuroReport on June 7, 2023.
The research team, which included Dr. Masahiro Sano (currently affiliated with Tohoku University) and Dr. Hikaru Iwashita (currently affiliated with Kansai Medical University), examined the effects of three compounds on memory formation; these compounds were melatonin, a hormone secreted by the pineal gland located in the brain; N1-acetyl-5-methoxyquinuramine (AMK), melatonin's biological metabolite; and ramelteon, a drug that binds and activates the melatonin receptor.
Initial experiments conducted on male mice clearly showed that the administration of melatonin, ramelteon, or AMK at a dose of 1 mg/kg facilitated the formation of long-term memory. The researchers did not investigate the effects of the three compounds on female mice to avoid any likely data variability resulting from the reproductive cycles occurring in female mammals.
Prof. Chiba concludes, "Our findings suggest that melatonin is involved in promoting the formation of long-term object recognition memory by modulating the phosphorylation levels of memory-related proteins such as ERK, CaMKIIs, and CREB in both receptor-mediated and nonreceptor-mediated signaling pathways."
Heat therapy boosts mitochondrial function in muscles
Brigham Young University, July 31, 2023
A new study finds that long-term heat therapy may increase mitochondrial function in the muscles. The discovery could lead to new treatments for people with chronic illness or disease.
Mitochondria, the "energy centers" of the cells, are essential for maintaining good health. Exercise has been shown to create new mitochondria and improve function of existing mitochondria. However, some people with chronic illnesses are not able to exercise long enough--previous research suggests close to two hours daily--to reap the benefits. Rodent studies have suggested that heat exposure may also induce the production of more mitochondria.
Researchers from Brigham Young University in Utah studied 20 adult volunteers who had not participated in regular exercise in the three months prior to the study. The research team applied two hours of shortwave diathermy--a type of heat therapy generated by electrical pulses--to the thigh muscles of one leg of each person every day. The researchers based the six-day trial of heat on the minimum amount of exercise needed to measure changes in muscle, or about two hours each day. They designed the treatment to mimic the effects of muscle heating that occurs during exercise.
Mitochondrial function increased by an average of 28 percent in the heated legs after the heat treatment. The concentration of several mitochondrial proteins also increased in the heated legs, which suggests that "in addition to improving function, [repeated exposure to heat] increased mitochondrial content in human skeletal muscle," the research team wrote.
"Our data provide evidence to support further research into the mechanisms of heat-induced mitochondrial adaptations," the researchers explained. People who are not able to exercise for long periods of time due to their health may benefit from [heat] treatments.
Too young for arthritis? 15% of global population over age 30 have condition
Institute for Health Metrics and Evaluation (US), August 21, 2023
Arthritis is just a problem for the elderly, right? Not so fast. A recent study finds that osteoarthritis affects 15 percent of individuals over the age of 30 worldwide. Contributing factors include obesity, as well as an aging and growing global population. Remarkably, excess weight is responsible for 20 percent of these cases. Moreover, for those over 70, osteoarthritis ranks as the seventh leading cause of years people live with a disability.
Experts forecast that by 2050, one billion people will be afflicted by this condition. Women tend to be more susceptible than men. The most commonly impacted areas include the hands, hips, knees, and other joints like the shoulders and elbows. By 2050, estimates predict a 78.6-percent increase in hip pain cases, 75 percent in the knee, 50 percent in the hand, and a staggering 95.1-percent increase in other areas.
This research, led by the Institute for Health Metrics and Evaluation (IHME) in Seattle, assessed three decades of osteoarthritis data from over 200 countries. In 1990, the global count was 256 million individuals with osteoarthritis. By 2020, this number skyrocketed to 595 million, marking a 132-percent increase from 1990. The dramatic rise can be attributed to three primary causes: aging, population growth, and the obesity epidemic.
The team’s findings underscored the mounting influence of obesity over time as its rates have soared. They estimate that effectively addressing obesity could reduce the osteoarthritis burden by one-fifth.
Decreased acetyl-L-carnitine levels associated with depression
Stanford University, July 30 2023
An article that appeared in the Proceedings of the National Academy of Sciences reported a link between low levels of acetyl-L-carnitine and a greater risk of depression.
Acting on the findings of animal research conducted by lead author Carla Nasca, PhD, the researchers recruited men and women between the ages of 20 and 70 years who had been admitted to Weill Cornell Medicine or Mount Sinai School of Medicine for treatment of acute depression. Clinical assessments were conducted upon enrollment and blood samples were analyzed for levels of acetyl-L-carnitine.
In comparison with levels measured in blood samples provided by 45 demographically matched healthy men and women, acetyl-L-carnitine blood levels in depressed subjects were substantially lower. Acetyl-L-carnitine levels were lowest among depressed patients who had severe symptoms, a history of treatment resistance, or early onset disease. Having a history of childhood abuse was also associated with low acetyl-L-carnitine levels.
"We've identified an important new biomarker of major depression disorder,” Dr Rasgon stated. “We didn't test whether supplementing with that substance could actually improve patients' symptoms. What's the appropriate dose, frequency, duration? This is the first step toward developing that knowledge, which will require large-scale, carefully controlled clinical trials."
Floatation Therapy for Specific Health Concerns
Medical University of South Carolina, August 6, 2023
We conducted a search of multiple databases using the following search terms: float, floatation therapy, floatation REST, isolation tank, stress, relaxation response, magnesium sulfate, transdermal magnesium, cortisol, pain, depression, anxiety, sleep, and addiction. The reviewed studies revealed benefits of floating, specifically regarding participants experiencing muscular pain, depression, anxiety, stress, and sleep disorders. Long-term benefits appear variable.
Traditionally, isolation tanks are enclosed to inhibit light and sound as much as possible and reduce all incoming stimuli. The float experience minimizes sensory signals including visual, auditory, olfactory, thermal, tactile, and gravitational. The studies discussed were conducted with the combination of water and Epsom salt. The salt-saturated water in most commercial centers is cleaned with a filtration system that runs between each session, in addition to manual skimming and treatment with ultraviolet light, hydrogen peroxide, and ozone. Generally, a float session lasts for 60 minutes, although it can be shorter or longer.
The benefits of magnesium sulfate (MgSO4), better known as Epsom salt, are well known. The World Health Organization (WHO) lists it as an essential medication.
A proposed mechanism of action of the aforementioned benefits of floatation therapy lies in the transdermal absorption of MgSO4. Given the selectivity of the stratum corneum layer of the skin and the ionic nature of elemental magnesium, it appears that specific lipophilic carriers are required for MgSO4 to cross the dermal layer into the circulation.
Among the benefits the analysis of studies suggest include:
Pain: Kjellgren and colleagues found a significant improvement with floatation therapy in those who experienced the most intense muscle pain (P=0.004), but there was no benefit found in participants who experienced lower levels of pain. There were 37 participants in this study, all of whom had chronic muscular pain of the neck and back regions. Individuals floated 9 times during a 3-week period. Of the 32 participants in this study, 22% became pain-free, 56% had improvement of pain, 19% experienced no increase or decrease of pain, and 3% experienced worsening of pain.
Depression and Anxiety: At the Laureate Institute for Brain Research in Tulsa, Oklahoma, researchers have extensively studied floatation therapy, particularly in the areas of depression and generalized anxiety disorder (GAD). One study involving 50 participants at LIBR examined the anxiolytic and antidepressant effects of floating. Results showed a significant reduction in anxiety among participants, regardless of gender. All changes were significant. Anxiety and stress-related disorders in this study included post-traumatic stress disorder, generalized anxiety disorder, panic disorder, agoraphobia, and social anxiety disorder. In addition to reduced anxiety, there was a significant improvement in mood characterized by “serenity, relaxation, happiness, positive affect, overall well-being, energy levels, and feeling refreshed, content and peaceful.”
Stress: Research generally finds floatation therapy to be beneficial for stress reduction. The relaxation response (which is associated with the parasympathetic nervous system) occurs when floating, lowering blood pressure and lowering cortisol levels in some studies.
Sleep: People have used floatation therapy to aid with sleep. Since magnesium is a common supplement used to aid with sleep, this is a logical area of float research interest. In a study looking at 19 athletes and floating, participants not only had improved athletic performance recovery, but also experienced significant improvements in having “deeper sleep, fewer awakenings during the night, and a sense of renewed energy upon awakening in the morning.”
