Longevity principle #1. How to sync with your daily biological clock to live longer?

This article was originally published on medium.com on February 1st, 2020.

Reading time: 13 min

Disclaimer

This article is based on my research of information from publicly available sources and my personal experience. The information, opinions, and references provided in this article are for informational purposes only. This article is not a medical advise and is not intended to treat, diagnose or prescribe for any illness or condition. Please consult your doctor or healthcare provider for your specific diagnosis and treatment.

Longevity principles series

This is the 3rd article in the Longevity Principle series. In this article, we deep-dive into Longevity principle #1 looking at the what, the why, and the how of sync with your daily clock to live longer:

• The “What”: what we want for longevity
• The “Why”: what is often wrong and why this happens
• The “How”: what you could practically do and how it minimizes aging

TL;DR: summary recommendations

If you are only interested in practical recommendations, here they are below. Read on to learn about the recommendations in more detail and the science behind them.

The “What”: what we want for longevity

Humans, and other living beings, didn’t evolve in isolation from the environment. Our bodies learnt to regulate physiological processes in response to the external cues which include light, temperature, and redoxcycles, i.e., loss (reduction) and gain (oxidation) of electrons. We all have a built-in clock called a Circadian Rhythm — a natural cycle repeating approximately every 24 hours which controls gene expression, molecular pathways, cells, and tissues.

The Circadian Rhythm exists because we can’t have all biological functions running at the same time. Up to 20% of different genes can be turned on or off at different times of day.

One of the keys to longevity and health is to live in accordance with the Circadian Rhythm.

If you don’t follow the Circadian Rhythm, you stress your body in a bad way (you can also stress your body in a good way — that’s called hormesis). For example, if you stay awake for work for 3+ hours between 10:00 p.m. and 5:00 a.m. for more than 50 days a year (once a week), you are actually considered a shift-worker and your Circadian Rhythm is disrupted. It turns out, I was a shift worker for most of the 3 years I worked as a management consultant.

Circadian Rhythm disruption puts you at an increased risk of diabetes, cancer, Alzheimer’s, and other major diseases.

The Circadian Clock regulates many processes including the nutrient- or energy-sensing pathways, the energy metabolism pathway, cellular maintenance mechanisms, repair and cell division, cell communication, cell secretion, etc. Those processes are hard to measure and a more manageable way is to focus on the three key phase markers of a circadian rhythm:

• Melatonin (sleep hormone) secretion by the pineal gland. Melatonin is a strong antioxidant which is often called a scavenger of free radicals. Melatonin starts to secret with sunset (~6 pm), peaks in the middle of the night, and declines in the morning with sunrise (~6 am).
• The plasma level of cortisol (“stress” hormone). Cortisol is at its highest level in the morning (6–9 am, usually ~30 minutes after waking up). Importantly, the hunger hormone, ghrelin, is at its lowest level at ~9 am. The reason cortisol is highest in the morning is that it helps pump glucose from your liver and muscles to set you up for the day.
• Core body temperature minimum. The core body temperature is at it lowest (~36.4°C) at 2–6 am. The temperature goes as high as 37.5 °C from 10 am to 6 pm.

Generally, you need to have a health routine — nutrition, environment, supplements, and physical activity — which keeps the circadian phase markers at where they need to be according to the circadian rhythm.

So here’s what you want for longevity:

• High melatonin levels at night and peaking in the middle of the night. Melatonin has been shown to activate the SIRT1 longevity pathway.
• Well functioning glymphatic system. It cleans amyloid plaques from the brain at night to prevent inflammation. The glymphatic system was discovered relatively recently in 2012 and has provided a major breakthrough in understanding how we clean waste from the brain and the importance of sleep.
• High (but not too high) levels of stomach acid at night. Stomach acid levels peak between 10 pm and 2 am. It’s not exactly clear why stomach acid peaks at night but it could be a way to fight inflammation: (1) to clean stomach from bacteria and pathogens while the stomach is at rest and (2) to prevent bacteria and pathogens from reaching intestines which activity slows down at night.
• Low core body temperature at night. It keeps the body at a low basal metabolic rate meaning that your body needs less energy (fewer calories) to support itself. The reasons for this are not exactly clear but it might have happened evolutionary because there was less food in general and having a period with low energy needs was beneficial. It’s important for longevity because a low metabolic rate increases mitochondrial membrane potential and activates UCPs (uncoupling proteins) via increased ROS (reactive oxygen species, aka free radicals) production. In turn, UCP activation may reduce ROS production — that’s how we can become a little more like birds.

Low core body temperature at night reduces leakage of free radicals — that’s how we can become a little more like birds.

• Low ghrelin (hunger hormone) and high leptin (satiety hormone) at night and in the morning keeping the hunger down. It promotes longevity by maintaining good insulin sensitivity. Here’s how: (1) Sleep reduces the production of ghrelin levels, likely so that we don’t wake up at night hungry; (2) Conversely, ghrelin levels rise when sleep is deprived; (3) High ghrelin stimulates growth hormone (GH) secretion which instructs your body to slow down glucose metabolism to maintain glucose in the blood; (4) Elevated glucose levels in the blood is a marker of your body becoming less sensitive to insulin. Some studies directly demonstrate that infusion of ghrelin decreases insulin signaling in the liver of the rat making rats less sensitive to insulin. Overall, I must admit that the relationship between ghrelin and insulin is complex and studies are often inconclusive or contradicting, partly because it’s difficult to have comparable setups in different experiments. But it’s clear that ghrelin and insulin secretion and glucose metabolism are regulated by the circadian rhythm and ghrelin plays a critical role in glucose metabolism.

The “Why”: what’s often wrong and why

For the majority of us, our bodies do not follow the above mechanisms, often because of our lifestyle choices.

What’s often wrong with our biological clocks and why?

• Low melatonin secretion at night disrupting sleep. Why? Excess blue light exposure during the day, before bed, and at night is a major reason. Our bodies are equipped with light sensing proteins called melanopsin located in the retinal cells. These proteins are most sensititve to blue light (and less sensitive to red light) and will tell the the brain it is day. The melanopsin cells are directly connected with the suprachiasmatic nucleus (SCN), the master clock in our bodies. The SCN is located at the hypothalamus, one of the key control parts of the brain, which controls hunger, satiety, sleep, stress response and more. So when you are exposed to blue light (your cell phone, laptop, LED lights at home, bright lights on the street on at a grocery store), the SCN cells will think that is day and will tell the pineal gland to stop producing melatonin. Your sleep will be disrupted and SIRT1 longevity pathway would not get upregulated as it should normally at night.
• Elevated cortisol levels before bed disrupting sleep. Why? Too much stress and late workouts (or possibly watching horror movies). The lowest cortisol level typically occurs around midnight and then starts to climb to get you ready to wake up, peaking in the morning. If you work out late or worry too much, you may have trouble falling asleep.
• Disrupted glymphatic system leading to accumulation of amyloids and brain inflammation. Why? Eating less than 3–4 hours before bed. Glymphatic system is primarily active when we sleep and is almost inactive during wakefulness. If you eat too soon before going to bed, more blood will flow to your gut instead of flowing to the brain. The glymphatic system will be disrupted and amyloid plaques and other toxins will accumulate in the brain. Dr. Dale Bredesen’s protocol for reversing cognitive decline and fighting Alzheimer’s diseaserecommends eating last meal at least 3 hours before bed. Dr. Steven Gundry recommends at least 4 hours.
• Excessive level of stomach acid leading to acid reflux. Why? Eating less than 3–4 hours before bed. As discussed above, stomach acid levels increase at night — they may be 5 times higher than in the morning. At the same time, saliva production at night is up to 10 times lower than during the day. Daytime saliva production is higher to neutralize stomach acid if it comes through our esophagus into our mouth. In addition, when food is consumed late, our stomach produces significantly more (by about 2 times) acid than during the day. So when you eat late, there is not enough saliva in your mouth to neutralize the stomach acid which is excessively high with night-time eating. Snacking actually has the same effect because it triggers the full digestion process which is a 2–4 hour cycle. In addition, because you lay down at night, the stomach acid flows up to the esophagus instead of being pulled down by gravity during the day. As a result, you may develop acid reflux and heartburn. Then you start taking proton pump inhibitors which eventually lead to leaky gut syndrome among other issues. Dr. Satchin Panda, one of the leading experts in the circadian rhythm research, describes this is detail in his excellent book “The Circadian Code”.
• High core body temperature at night leading to increased metabolic rate and disrupted sleep. Why? High room temperature, late workouts or eating too much or too late. Our core body temperature cools down by almost 1°F before we can fall asleep. If you eat late, the blood flows to the gut to aid digestion and your skin temperature stays high. As a result, you have trouble falling asleep or wake up at night.
• High ghrelin (“hunger”) and low leptin (“satiety”) levels in the morning leading to hunger and insulin resistance. Why? Not enough sleep. Some studies show that even a single night of sleep deprivation increases ghrelin levels. As discussed above, higher ghrelin levels not only make you more hungry but also instruct your body to keep a higher blood glucose concentration which is the opposite of what you want.
• Adrenaline spike at night (“danger” hormone) due to a sharp drop in glucose at night leading to middle-of-the-night insomnia. Why? High-sugar meals late before bed lead to elevated glucose levels for 2 reasons: (1) melatonin inhibits insulin secretion at night and (2) pancreas reduces insulin production at night. Elevated glucose levels suddenly drop in the middle of the night leading to an adrenaline spike — that’s called reactive hypoglycemia and it happens with non diabetic people too.

Yep, that’s a lot of scary and stressful stuff for the body from seemingly normal activities — looking at your phone at night, eating late dinners or snacking, being stressed, etc.

The “How”: what you can practically do and how it minimizes aging

The recipe to fix these issues is quite simple. Let’s brake them down in groups — environment, accessories, supplements, nutrition, and physical activity.

Environment

• Keep the room temperature at 60–67° F (15.5–19.5° C). When your skin cools down, the blood flow to the skin to keep it warm. This helps to fall asleep easier. As mentioned above, the reasons why the core body temperature has to go down at night aren’t completely clear but it’s likely because it requires less energy to sustain the body. However, the benefits are clear — it has been proven that sleeping at 19° C room temperature improves insulin sensitivity.

Sleeping at 19° C room temperature has been shown to improve insulin sensitivity

• Consider getting an electric cooling blanket (e.g., BedJet, ChiliPad, etc.). That’s especially useful, if you and your partner prefer different temperatures.
• Use blackout curtains. There is so much junk light from the street, especially if you live in a big city, that using blackout curtains is a must.
• Turn off or dim the lights at least 2 hours before sleep. My wife and I have most of our lamps on the floor anyway but in addition limit our exposure to light by turning them off early. Again, there is so much light outside that it’s usually enough for night time activities. In addition, you can save on the energy bills.
• Switch to longer wavelength light sources. You can use incandescent light bulbs or red LED instead of blue light LED. Shorter wavelengths (such as in LED light bulbs) disrupt melatonin secretion and damage retina. We changed all light bulbs at home to incandescent. It may add a few dollars to the energy bill but will definitely keep you more healthy.
• Aim for 7–9 hours of sleep. Sleep is important for many reasons. Let’s talk about just two. The first reason is learning and memory consolidation. There are 3 stages of sleep — light sleep, deep sleep, and REM sleep. If we simplify, deep sleep restores your body while REM sleep restores your mind (learning and memory consolidation). Typically, we have 3–5 cycles of REM sleep per night, happening every 90–120 minutes. The later REM cycles last longer so if you sleep less, your learning and memory consolidation are at risk. The second reason is hunger and calories consumption. Ken Wright’s sleep lab demonstrated that reducing sleep from 8 hours to 5 hours leads to consistent consumption of more calories. The reason is not that the body needs more calories if it’s awake for longer but rather that shorter sleep stimulates secretion of ghrelin, the hunger hormone, which we discussed before.

Accessories

• Wear blue light blocking glasses at least 30–60 min before bed. Cheap red safety glasses such as these ones could do the job (can’t speak of their quality though). I use the Twilight Classic by Dave Asprey’s TrueDark brand because they are comfortable and provide a full protection from the junk light. My wife sometimes even sleeps in them — that’s how comfortable they are. Blue-light-filtering glasses have also been shown to reduce the incidences of migraine and the duration of the attacks.

Supplements

• Consider supplementing with low dose melatonin for restless sleep.The most effective dosage to treat insomnia and not make you sleepy the next day is 0.3 mg — that’s 10 times less than a regular tablet. It’s best not to take melatonin after a meal because food increases blood glucose and melatonin inhibits the decline in blood glucose to the normal level. Personally, I rarely take even this small dose of melatonin because that’s not necessary if you fix the other problems.
• Supplement with Ashwagandha. Ashwagandha is an adaptogen meaning that it balances your cortisol levels instead of making it too low. There are 2 major types of Ashwaganhda — Sensoril and KSM-66. If your goal is to calm down your stress response, you should opt for Sensoril before bed and possibly in the morning or during the day. Personally, I use KSM-66 daily in the morning because of its energy stimulating effect.

Nutrition

• Eat your last meal or snack no later than 3–4 hours before bed. This will support your glymphatic system, maintain healthy stomach acid levels, and keep your body temperature lower. Interestingly, Dr. Satchin Panda describes in his book that the optimal eating window is 10-hours, so if your first meal is at 8 am, your last meal should be no later than 6 pm. If you go outside the 10-hour eating window, then the digestion takes a lot longer because the body is redirecting resources from the other tasks it has to do. In addition, gut motility has low activity at night, so when we eat late, we can develop indigestion because the food moves slowly through the GI tract.
• Stay away from high-sugar meals and beverages for dinner such as high glycemic index fruits, deserts, and sweetened drinks. High sugar meals can wake you up at night, decrease your insulin sensitivity, and are also more likely to make you fat (compared to consuming in the morning or during the day) because at night the body is designed to run on fats. Though it’s best to exclude the high-sugar stuff from your diet completely for the reasons we’ll discuss in the upcoming articles.

Physical activity

• Finish physical exercises 1.5–2 hours before sleep. That should give some time for your cortisol levels and body temperature to go down.
• Meditate for 10–20 minutes a day. Some studies have demonstrated that mindfulness meditation decreases cortisol levels. I meditate daily for 20 minutes in the morning and can feel the difference in my sleep if I don’t.

In practice

Walking before bed helps me unwind but I like to keep my junk light blocking glasses on to avoid disruption of melatonin secretion.

While raccoons in my neighborhood clearly think that I look crazy, I don’t care because my biological clocks work well.

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