Long-term Cognition, Longevity, Mental Health, and Immunity via a strong, robust Circadian Oscillation

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes.

 

The internal body clock sets the timing for many circadian rhythms, which regulate processes such as

• Sleep/wake cycles
• Hormonal activity
• Body temperature rhythm
• Eating and digesting

 

Caloric restriction itself extended the lifespan of mice by 10%; when the fasting time was added, the lifespan was increased to 20%; and when the feeding time was aligned to the active period, the lifespan was further extended to 35%, demonstrating that when food intake is restricted to an appropriate time of the day there is an additional benefit to caloric restriction and fasting on lifespan.

 

“If your circadian clock is not quite right for years and years — you routinely suffer from disrupted sleep at night and napping during the day — the cumulative effect of chronic dysregulation could influence inflammatory pathways such that you accumulate more amyloid plaques”.

 

Dr. Satchin Panda explains his discovery of how food timing drive the circadian rhythm. As Dr. Panda explained in this video, light timing affect the brain’s rhythm, while food timing affect the rhythms in the rest of the body. Both should be in sync for optimum health.

A strong, robust, circadian oscillation may help one avoid dementia 

Synchronizing rhythms may delay the onset of neurodegenerative disease such as AD. A weak or misaligned circadian rhythm, can, over time, be causative of cognitive decline.

 

Circadian derangements/disturbed sleep feed the risk of developing AD. Dissociation between the output of the circadian clock and external environmental cues is a major cause of human cognitive dysfunction.

 

Proper circadian protein function is important in the maintenance of neuronal integrity. Here is why: Circadian rhythms modulate blood-based barrier (BBB) integrity through regulating oscillations of tight junction proteins, assisting in functions of the neurovascular unit (NVU), and modulating transporter functions.

 

A robust circadian oscillation may minimize neuroinflammation.

 

Circadian dysfunction precedes Alzheimer’s symptoms. Demonstrated in mice.

 

Rats in which the circadian rhythm was messed up with continuous light for four months showed disrupted metabolic profiles, suggestive that their digestive systems may also have been adversely affected by the disrupted circadian rhythms. The level of soluble Aβ in the brain was also significantly higher in these rats compared to the controls, and they experienced down-regulation of anti-aging gene Sirt1 and up-regulation of the neuronal damage markers. Circadian rhythm disruption due to chronic light exposure caused memory and cognitive deficits in the rats. Collectively, these findings were suggestive of an AD-like phenotype.

 

There is a daily oscillation in Aβ42 clearance that was lost in cells without a circadian rhythm. We established the underlying cause of this oscillation was the circadian control of cell surface molecules, heparan sulfate proteoglycans, which have previously been shown to play a role in the regulation of Aβ42 clearance. We further showed that this regulation was specific to Aβ42, demonstrating a mechanistic link underlying the connection between the disruption of circadian rhythms and AD.

 

In addition to being a key regulator of the diurnal cycle, the circadian clock might also suppress oxidative stress and synaptic damage. For example, a reduced level of BMAL1, one of the circadian regulating factors, is thought to cause neurodegeneration, as evidenced by the astrogliosis, oxidative damage, and synaptic damage in Bmal1 knockout mice.

 

In animal models of Alzheimer’s disease, a basal circadian rhythm that controls macroautophagy may be necessary to limit cognitive decline and amyloid deposition. Neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease may progress in the setting of altered circadian rhythm dysfunction.

 

 

 

In patients with Alzheimer’s disease, rhythmic methylation of BMAL1 has been found to be changed in the brains of patients with Alzheimer’s disease, suggesting that alterations in the DNA methylation of clock genes may contribute to cognitive loss and behavior changes in individuals with Alzheimer’s disease.

 

Circadian signalling is greatly disturbed in aging. There is a clear reduction in the amplitude of the circadian electrical rhythm, suggesting a weakening of the output timing signal. Other brain areas and organs not only show aging-related deficits in their own local clocks, but also receive a weaker systemic timing signal.  Consequently, chronotherapeutic interventions should aim at strengthening overall synchrony in the circadian system using life-style and/or pharmacological approaches.

Other brain disorders are linked to a dysfunctional circadian system.

 

Circadian dysfunction injures via poor sleep efficiency. Quality sleep is essential to keep cognitively intact. See this post on sleep.

Circadian dysfunction injures via altered gene expression. In mice, time-restricted eating influences gene expression across more than 22 regions of the body and brain. Nearly 40% of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. Hormones coordinate functions in different parts of the body and brain, and hormonal imbalance is implicated in many diseases from diabetes to stress disorders. The results offer guidance to how time-restricted eating may help manage these diseases.

 

Minimizing blue light in the evening will maximize endogenous melatonin.

 

“Shift work, especially rotating shift work, confuses our body clocks and that has important ramifications in terms of our health and well-being and connection to human disease,” said David Earnest, professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M University College of Medicine. “When our internal body clocks are synchronized properly, they coordinate all our biological processes to occur at the right time of day or night. When our body clocks are misaligned, whether through shift work or other disruptions, that provides for changes in physiology, biochemical processes and various behaviors.” Eating meals during daylight hours may avoid some hazards of night shift work. The timing of calorie intake (eating-fasting patterns) is a modifiable lifestyle factor that has the potential to lessen the burden of circadian disruption and support health in shift workers. Time-restricted eating (TRE) is a behavioral intervention that limits the time of daily caloric intake to a consistent window of 6–12 h, without overtly attempting to limit energy intake. A 10-h time-restricted eating is feasible for shift workers on a 24-h schedule.

 

It’s this internal misalignment, this state of desynchrony between and within organs that occurs during jet lag, that is responsible for the adverse impact on neurogenesis – and, they suspect, other adverse health effects from circadian disruption. Circadian misalignment is critical in jet lag. Dr. Satchit Panda has advice to avoid jet lag.

 

Circadian dysfunction is strongly implicated in depression

From Harvard Health:

Multiple studies show an increased prevalence of depression in night-shift workers. One meta-analysis showed that night-shift workers are 40% more likely to develop depression than daytime workers. Conversely, circadian rhythm disturbances are common in people with depression, who often have changes in the pattern of their sleep, their hormone rhythms, and body temperature rhythms.

From this wonderful interview by Dr Rhonda Patrick with Dr. Satchin Panda, here is the following:

 

Every organ in our body has a clock that optimizes the function of that organ. These peripheral clocks keep their own time, but they are also affected by the timing of food intake.

 

A study of 49 day-shift office workers (27 in windowless workplaces and 22 in workplaces with windows) showed that, compared to workers in windowless offices, those with windows received 173 percent more natural white light exposure during work hours and slept an average of 46 minutes more per night. Workers who got more sunlight also tended to be more physically active according to this study. And an additional analysis of overall quality of life suggests that they’re generally happier, too.

 

Dr. Panda’s research in mice has demonstrated that time-restricted eating has health benefits that may include reductions in fat mass, improvements in glucose tolerance and insulin sensitivity, increases in lean muscle mass, lower inflammation, improved heart function with age, increased mitochondrial volume, especially in the liver and brown fat, and an increase in ketone body production. Protection from mild age-related hepatic steatosis (fatty liver). In the high-fat group this effect was especially robust: they experienced a 53% reduction in triglyceride accumulation.

 

For those who exercise and practice intermittent fasting, consuming protein powder outside of one’s normal eating window may be beneficial. Pre-sleep casein protein intake (30–40 g) provides increases in overnight muscle protein synthesis and metabolic rate without influencing lipolysis (the breakdown of fats). Protein powder does not trigger an insulin response, so it is unlikely to screw up a circadian oscillation.

 

 

Melatonin receptors are found in pancratic islet cells, where is signals and it inhibits insulin secretion. Insulin sensitiviy is very different between day and night. Calories taken early in the day may not have the same effect as calories taken late in the day. The melatonin receptor can inhibit insulin secretion. So: (dark) candlelight dinners may not be such a good idea.

 

A Spanish study found that delaying (3 pm) “lunch” cause participants to lose less weight than those who did not delay lunch. A study of fruit flies found similar benefits, even when introduced late in life. Additional information on obesity and the circadian clock is in this blog post on obesity.

 

Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm. The finding: Early time-restricted eating improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

 

This randomised controlled trial was conducted of overweight adults with type 2 diabetes (n = 120). The results suggest that 10-h restricted feeding improves blood glucose and insulin sensitivity, results in weight loss, reduces the necessary dosage of hypoglycaemic drugs and enhances quality of life. It can also offer cardiovascular benefits by reducing atherosclerotic lipid levels.

 

This study in mice showed that an every-other-day fasting regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis.

 

Time restricted eating promotes gut bug diversity.

Autism Spectrum Disorder

We found that increased impairments in social and executive function occurred with increased sleep–wake disturbances, particularly those related to the circadian rhythm, suggesting that these perturbations/disruptions in the sleep–wake cycle could be connected to autism spectrum traits.

 

Alterations in circadian sleep–wake rhythm have frequently been reported in autism. More specifically, reduced total sleep and longer sleep latency as well as nocturnal and early morning awakenings are often observed in individuals with ASD. Furthermore, prior studies on melatonin in autism have all reported abnormalities in melatonin secretion. In addition, abnormalities in cortisol circadian rhythm have also been reported in autism. In particular, significantly higher frequency of absence of circadian variation in melatonin and cortisol levels was observed in individuals with autism compared to typically developing controls.

 

Studies on sleep showed how ASD subjects typically report more problems regarding insufficient sleep time, bedtime resistance and reduced sleep pressure. A link between sleep difficulties and irritability, deficits in social skills and behavioral problems has been noted. Among the mechanisms implicated, alteration in genes related to circadian rhythms, such as CLOCK genes, and in melatonin levels were reported. ASD subjects also showed altered hypothalamic pituitary adrenal (HPA) axis and autonomic functions, generally with a tendency towards hyperarousal and hyper sympathetic state. Some of these biological alterations in ASD individuals were not associated only with sleep problems but also with more autism-specific clusters of symptoms, such as communication impairment or repetitive behaviors. Among the available treatments melatonin showed promising results.

 

In ASD, the nocturnal secretion of melatonin is low. Intellectual disabilities are associated with melatonin abnormalities. Melatonin use in ASD children is associated with improvement of communication, stereotyped behaviors, anxiety and social withdrawal.

 

Based on the above information, those on the autistic spectrum might do well to adopt a circadian-friendly lifestyle: eat and vigorously exercise only early in the day and avoid blue light/overhead light in the evening hours.

 

There is additional information on circadian health at the bottom of this blog post on avoiding diabetes.

 

This site may be helpful: http://www.mycircadianclock.org/.