Circadian Rhythm

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Intro to Circadian rhythm

Our body keeps time. The rhythms of our body roughly match that of the earth’s rotation. These rhythms are cycles the body follows within a 24 hour day and it repeats these rhythms day after day. The circadian system is a network of interacting neural and hormonal pathways that entails more than driving the sleep-wake cycle, they include hormonal activity, body temperature, digestion, and immune function. Every organ, even every cell, has its own daily timed circadian rhythms, certain proteins interact with cells in the body, instructing them to be more active or to slow down.

Liken circadian rhythm as being like your dog or cat that expects to get fed at a certain time every day and lets you know if the regular timing isn’t met. Just like your pet, your body gets out of sorts when certain events don’t happen when expected.

Being out of sync with one’s circadian rhythms (circadian arrythmia) has been associated with obesity, cardiovascular disease, diabetes, gastrointestinal problems, neurodegenerative disorders (including dementia), skin issues and more.

How circadian rhythm works

Light enters the eyes (even through closed eyelids during sleep), stimulating a signal in the back of the retina and down a nerve tract to the circadian clock in the brain.

Add Graphic - light to eye to brain “Light enters the eye (even through closed eyelids during sleep) stimulating a signal in the back of the retina and down a nerve track to the circadian clock in the brain Source: Circadian Rhythms and Circadian Clock https://www.cdc.gov/niosh/emres/longhourstraining/clock.html"

Circadian photoentrainment is the process by which the brain’s internal clock becomes synchronized with the daily external cycle of light and dark. This process is mediated by retinal ganglion cells (RGCs) which are a type of neuron located near the inner surface of the retina of the eye. RGCs are separate from rod and cone photoreceptors of the eyes. RGCs send signals to the region of the brain that houses the circadian pacemaker.

The body’s master clock is a structure called the suprachiasmatic nucleus (SCN). The SCN contains about 20,000 nerve cells and receives the input from the eyes.

As the eyes perceive the bright light of day or the darkness of night, the SCN tells the cells to act accordingly. Light is what keeps in sync (or disrupts) the circadian rhythm within a 24-hour day.

Chemicals in the brain adjust a number of factors in the body, such as:

• hunger
• temperature
• arousal and awakeness
• mood

The body’s circadian rhythms control the sleep-wake cycle. As darkness sets in, the body’s biological clock instructs the cells to slow down. A key driver of the body’s circadian rhythms is melatonin, the sleepiness hormone. When the evening becomes dark, the hormone melatonin starts to rise and allows sleep to occur. Melatonin peaks around 2–4 A.M. and then reduces by morning, when the hormone cortisol starts to be released, allowing for wakefulness.

But the circadian rhythms control more than sleepiness-wakefulness, and the end result directly affects our health.

Circadian Rhythm and APOE4

APOE4 is the ancestral gene. For the vast majority of time, all humans were ApoEε4/4 as were the primates we evolved from. The other two alleles, ε3 and ε2, arose recently in evolutionary terms. As the ancestral gene, it’s been suggested that ApoE4s are ill-adapted to modern lifestyle/diet. Without electrical light, high-speed travel, constant food availability and around the clock work-life schedules, our ancestors' were in circadian harmony with their environment. Our ancestors were active during daylight hours and resting/sleeping during the darkness of night. But modern lifestyle ignores this day/night harmony and instead is filled with artificial light, ingested stimulants, environmental irritants, late night snacking, around the clock work demands and added stress.

Chronic circadian misalignment is associated with an increased risk of metabolic syndrome, cardiovascular disease, neurological conditions, and cancer. ApoE4s are particularly concerned with shortened longevity, cardiovascular issues, and Alzheimer’s Disease.

With particular emphasis on Alzheimer’s Disease, numerous studies have shown that cognitive processing is gated over the circadian cycle and memory retrieval is disrupted when the organization of body clock timing is compromised thereby contributing to cognitive deficits.

Circadian dysfunction not only contributes, but is also a symptom in Alzheimer’s Disease. Individuals with Alzheimer’s Disease often confuse morning and evening with sleep disturbances. They also often act differently in the fading light of late afternoon or early evening a condition called sundowning, or sundown syndrome.

Add Graphic - self feeding loop “The self-reinforcing loop of disrupted circadian rhythm in Alzheimer’s Disease. Source: Circadian clocks, cognition, and Alzheimer’s disease: synaptic mechanisms, signaling effectors, and chronotherapeutics, (Kari R. Hoyt & Karl Obrietan, 7 May 2022) https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-022-00537-9?fbclid=IwAR11GYivCStCnfXIVqO1mQ-AOxy-2Ii_zCwaigjF2oXvUQ8MjEWHZJFYCyc"