Did you know that your body has its own internal clock? This “circadian rhythm” is responsible for regulating many different bodily functions, and can play a big role in your overall health. The start of Daylight-Saving Time this month is a good reminder to talk about circadian rhythm—the internal clock that governs our sleep-wake cycles. Most of us are familiar with the yearly ritual of setting our clocks ahead one hour, but do you know what circadian rhythm is and why it’s important? Understanding your own circadian rhythm and how to work with it can be an important part of maintaining good health. In this blog post, we’ll discuss what circadian rhythm is, how it works, and some ways that you can optimize your own rhythm to improve your health. Stay tuned!

Circadian rhythm is a natural, physiological process that regulates many different bodily functions.  It is controlled by a part of the brain called the suprachiasmatic nucleus (SCN), which responds to light and dark signals. These signals help to synchronize our body’s clocks with the 24-hour day-night cycle.

The circadian rhythm has a huge impact on our health. It can affect everything from our energy levels to our sleep quality. How rhythmic or not your circadian rhythm is can have wide-ranging effects on your health, including but not limited to the following:

Heart Health

Key functions of cardiovascular health work on a circadian rhythm[i]. When there is a disruption to our circadian rhythm, it can increase our risk for a whole host of cardiovascular problems. Heart attack, stroke, high blood pressure and irregular heartbeat have all been linked to circadian rhythm disruption. A 2019 research study found a higher risk of heart attack after both time changes, but particularly during daylight saving. It is believed that the sudden shift in light and dark can confuse the SCN and cause it to send mixed signals to the heart.


The body’s metabolic rate is also tied to its circadian rhythm. When the rhythm is disrupted, it can lead to weight gain, insulin resistance and other metabolic problems. People who have a more regular circadian rhythm are more likely to have a healthy weight, while those with disrupted rhythms are more prone to obesity and metabolic disorders. Metabolic homeostasis, the body’s ability to maintain a healthy weight, is regulated by the circadian rhythm.[ii]


The quality of our sleep is also closely tied to our circadian rhythm[iii]. The more regular and in sync our rhythm is, the better our sleep tends to be. People with disrupted circadian rhythms often suffer from insomnia, restless leg syndrome and other sleep problems. Poor sleep at the systems level can lead to a number of health problems, including obesity, diabetes and heart disease. There are specific disorders with known links to the central clock. These are known as circadian rhythm sleep disorders (CRSDs) and include:

Delayed Sleep Phase Disorder (DSPS):  People with this disorder have a hard time falling asleep and waking up at conventional times. They tend to go to bed late and wake up later than most people.

Advanced Sleep Phase Disorder (ASPD): People with this disorder fall asleep early and wake up very early, often before sunrise.

Irregular Sleep-Wake Syndrome (ISWS):  People with this disorder have no real pattern to their sleep and wake times.

Jet Lag:  This is a temporary disruption of the circadian rhythm that can occur when traveling across time zones.

Shift Work Disorder:  People who work at night or rotate shifts often have trouble adjusting their circadian rhythm to the new schedule.

Irregular Sleep-Wake Syndrome (ISWS):   People with this disorder have no real pattern to their sleep and wake times.


While the link between circadian rhythm and cancer is still being studied, there is some evidence that circadian rhythm disruption can increase the risk of cance[iv]r. One study showed that women who worked night shifts had a higher risk of breast cancer.[v] Another study found that people who slept fewer than six hours per night were more likely to develop colon cancer.[vi] More research is needed to determine the precise link between circadian rhythm and cancer, but the preliminary evidence is suggestive.

Blood-Sugar Regulation

The circadian rhythm also regulates blood sugar levels[vii]. When the rhythm is disrupted, it can lead to insulin resistance and type 2 diabetes. Studies have shown that people with regular circadian rhythms are less likely to develop type 2 diabetes, while those with disrupted rhythms are more prone to the disease.


Asthma is the result inflammation in the airways, which makes it difficult for you breathe.  In terms of circadian rhythm, asthma follows a “diurnal pattern” which refers to the regular daily fluctuations in symptoms. Asthma typically worsens during the day and is better at night. Research has shown that the disease path of asthma is closely linked to the circadian rhythm of certain inflammatory pathways.[viii]

Hormone Regulation

The circadian rhythm also regulates many hormones, including cortisol and melatonin. When the rhythm is disrupted, it can lead to hormone imbalance and a number of health problems. For example, people with disrupted circadian rhythms often have difficulty regulating their stress levels, which can lead to anxiety and depression. Melatonin is a hormone that helps regulate sleep-wake cycles. When the rhythm is disrupted, it can lead to problems with sleep and insomnia.


There are many ways to optimize your circadian rhythm and improve your health. Some tips include:

Daytime Light Exposure

Getting plenty of natural sunlight during the day is essential for keeping your circadian rhythm in check. Sunlight helps to synchronize the SCN and keep it aligned with the external environment. Make sure to get outside for at least a few minutes each day, even if it’s just to take a quick walk.

Blocking Light at Night

If you’re unable to get outside during the day, try to avoid exposure to artificial light at night. Blue light, in particular, can disrupt your circadian rhythm. Make sure to use blackout curtains or eye shades especially if you need to sleep in a room that has artificial light.

Staying on a Regular Schedule

Keeping a regular sleep schedule is one of the most important things you can do to optimize your circadian rhythm. Try to go to bed and wake up at the same time each day, even on weekends.

Eating a Healthy Diet

A healthy diet is also essential for keeping your circadian rhythm in check. Eat plenty of fruits and vegetables and make sure to get enough protein and healthy fats. Avoid eating processed foods and sugary snacks, which can disrupt your rhythm.

Exercising Regularly

There is an old saying that couldn’t be truer: “A tired dog is a good dog.”  Exercise is crucial for keeping your circadian rhythm in balance. Make sure to get at least 30 minutes of exercise each day, and try to do it at the same time each day whenever possible.

Managing Stress

Finally, managing stress is essential for keeping your circadian rhythm in check. When you’re stressed out, it can throw off your rhythm and lead to a host of health problems. Make sure to practice relaxation techniques such as yoga, meditation, and deep breathing exercises on a regular basis.

Caffeine Intake

Caffeine is a stimulant that can also disrupt your circadian rhythm. Try to avoid drinking caffeinated beverages late in the day, and try not to drink them at all if you’re struggling to get to bed.


The circadian rhythm is one of the most important patterns in your life and it has a significant impact on your health.  By understanding how this pattern works, you can make small changes to improve your well-being. We hope that this week’s blog post has helped increase your knowledge about circadian rhythms and their importance. Be sure to follow us next week for another informative blog post!









Your immune system is designed to distinguish between what belongs in your body (e.g., I like you, myself) and what doesn’t (e.g., I don’t like you, not myself). For this purpose, it uses specialized cells to carry information around the body about which substances are friends or foe. It does this by tagging these molecules with pieces of protein called antigens. These pieces of information are carried on specialized cells – white blood cells – and displayed to other white blood cells by the process of antigen presentation. Immune cells use this information about which things in your body, good or bad, belong and which don’t as a guide to perform different tasks such as killing invaders. Autoimmune conditions are conditions where the body’s immune system attacks its own tissues (and sometimes organs). Autoimmune conditions are increasing at an alarming rate yet diagnosing them can be tough. This week’s article will discuss the 5 basic components of autoimmune conditions.

Autoimmunity encompasses a diverse range of conditions that occur when something goes wrong with our immune system.  In fact, the immune system is meant to be a smart one. It receives information from our microbiome and has different cells that perform unique tasks – T-helper cells, cytotoxic T-cells, B-cells, etc. – all of which have a very particular purpose in their job description. This makes it tough for autoimmune conditions to sneak by undetected. Autoimmunity arises when something goes wrong in one of these components. When the immune system malfunctions, it starts to attack its own cells, tissues and organs. It can also lead to inflammation which is often autoimmune conditions are associated with excess amounts of systemic inflammation. Such conditions are referred to as autoinflammatory or autoinflammatory disorders.

Autoimmune conditions generally require 5 components: genetics, environmental factors, loss of gut-barrier function, an unruly immune system, and an imbalanced microbiome.

1. Genetics Our genetic code is made up of 46 chromosomes, including 22 pairs of autosomes (a chromosome that is not a sex chromosome) and one pair of sex chromosomes (X/Y). The sex chromosomes determine whether we develop male or female traits. Each cell in our body has the same DNA; however, different types of cells express different genes. For instance, liver cells only express the genes that play a role in liver function. The genetic code contains both “sensor” and “effector” information. Sensor information is expressed as recognition molecules called receptors and effectors are the responses generated by certain mechanisms when they bind to their receptors. Some of these receptor and effector mechanisms are enzymes and ion channels. Most cells in the body do not express receptors that recognize antigens (proteins that induce an immune response). However, some cells such as B-cells and T-cells — which play a key role in adaptive immunity — express receptors on their surface called immunoglobulins (antibodies). When an antigen binds to the B-cell receptor, the B-cell becomes activated and changes its gene expression to produce plasma cells. These plasma cells secrete antibodies that bind to the antigen. Then, other immune system cells aid in clearing the antigen out of circulation. The presence of these proteins on their cell surfaces is the first step in the immune response, which then triggers an adaptive response.

It has been suggested that genetics play a role in the development of autoimmune diseases, including lupus and rheumatoid arthritis. The risk of developing an autoimmune disease is increased if you have family members with one or more autoimmune diseases. Many genes are believed to be involved in autoimmune disease, and it is believed that certain genes make people more susceptible to developing an autoimmune disease. For example, celiac disease an autoimmune condition that affects the small intestine is thought to be strongly influenced by genetics. A person with celiac disease is at increased risk of having family members with celiac disease, especially if they are related through blood (inherited). While your genes play an important role, they do not have to be your health destiny.  You can make changes in your lifestyle that affect your genes. 

2. Environmental Triggers: Environmental triggers are stimuli that exist in their environment which cause them to become ill. Environmental triggers are generally defined as non-infectious agents or conditions, although some infections can also be included within this definition. Examples of environmental triggers include chemicals, allergens, medications, ultraviolet radiation, thermal conditions, pollution, etc. Some environmental factors are known to possibly trigger or worsen autoimmune conditions, including celiac disease and Hashimoto’s thyroiditis.[i] For example, gluten consumption has been identified as a possible triggering factor for autoimmune diseases, especially celiac disease. Some data even suggests that there is a higher prevalence of autoimmune conditions among those living in geographic regions where gluten consumption is more common. This means that people who live in areas with a high percentage of people who eat foods containing gluten (such as wheat or other grain products) may have an increased risk of developing an autoimmune condition, including celiac disease.

3.Loss of Gut-Barrier Function[ii]: Our gut-barrier function is a complex process that prevents unwanted substances from reaching our blood, lymphatic system and other areas of the body. Our body doesn’t want us to get sick, so there are mechanisms in place that work together to create this barrier. It has been suggested that the gut-barrier may be breached or damaged by environmental triggers, food ingredients or medications. This allows substances from the lumen of the intestine to enter our internal environment and trigger an autoimmune response. It is believed that the innate immune response in autoimmune conditions is created when our gut-barrier function is compromised and foreign antigens (antigens are fragments of proteins that induce an immune reaction) enter into systemic circulation. Inflammatory bowel disease (IBD) is a condition where there is a breakdown in gut-barrier function which results in an uncontrolled inflammatory response. The breakdown of the gut barrier may be due to genetic factors, environmental triggers or loss of mucosal integrity. Loss of gut-barrier function is common in autoimmune conditions, especially celiac disease and psoriasis.

4. An Unruly Immune System: The immune system has two main divisions that are responsible for protecting us from foreign invaders:   innate immunity and adaptive immunity. Innate immunity is our first line of defense against foreign invaders.[iii] It is non-specific and protects us by using physical, chemical and cellular barriers. The innate immune system reacts immediately to stop infection. This response takes place in all individuals, regardless of what organism or antigen has caused the stimulation. Innate Immunity usually stops an invasion within minutes to hours. Examples of this include fever, inflammation and the production of mucus. The second line of defense is our more specific adaptive immunity. In contrast to innate immunity, it takes days to weeks to fully activate. It works by creating a memory of the foreign invader and being able to recognize it if it were encountered again in the future. Adaptive Immunity, also known as T-cell mediated immunity, creates specific responses to antigens (the specific substance that causes the immune system to respond). Antigens can be proteins, such as those found on bacteria or viruses. They may also be tumor-associated proteins and transplant tissue antigens.

5. Imbalanced Microbiome: The human microbiome is a complex, vast and dynamic ecosystem of microbial and human cells that live in and on our bodies. We have an estimated 2-4 pounds of microbes living inside us, which is about the weight of a bowling ball. These microbes are made up of approximately 1000 different species from more than 39 major phyla. Our microbiota (the bacteria, viruses and fungi that live in or on our body) contains at least 160 times more bacterial cells than human cells. These microbial communities vary greatly and can be affected by many factors such as diet, genetics and environmental exposures. Bacteria within the microbiome produce enzymes and other chemicals which help to maintain health. The majority of these organisms exist in the gastrointestinal tract, where they synthesize vitamins, process carbohydrates and fats and degrade toxins and drugs. When our microbiome is imbalanced, this is called dysbiosis. Dysbiosis is when there is an abnormal composition of the microorganisms that comprise our microbiome. The microbiome can be disrupted by changes in diet, use of antibiotics and aging, among other things. It’s been estimated that over 50% of people with autoimmune conditions have alterations in their gut flora when compared to healthy individuals. Although researchers are still determining what a healthy microbiome looks like, it has been shown that the gut microbiota in patients with autoimmune disease is different from those who typically lack inflammation.

Institute for Human Optimization

We are seeing more a paradigm shift in healthcare.  At IfHO, we partner with you to become your health intelligence partner with the goal of optimizing your health. We accomplish this with our signature precision medicine approach. This may include functional, traditional, and/or naturopathic medicine. Our providers use a combination of therapies that are tailored to your specific needs with a health optimization goal. We believe that our Medical Team should make use of the latest scientific research to offer our patients personalized medicine, based on real data. We call this precision health and it is the future of healthcare.

Our focus is not only looking at the root cause, but also to measure, quantify and optimize the patient’s personal health. We take a preventative approach, personalized, and precise approach in helping our patients control their risk factors early on in order to avoid chronic illness down the road. Our team of medical providers use a comprehensive approach with every patient that comes into our office, looking at all aspects of health including lifestyle, environment and genetics. There is no generic one size fit all protocols. No two patients receive the same treatment plan since we work with each individual to create a personalized plan. We empower our patients with the right tools and information, so they can take control of their own health. This is the future of longevity!




Maryland Functional Medicine

Maryland Functional Doctor

Maryland Functional Physician


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Have you ever wondered why sugar makes everything taste better? Sweetness is one of the most sought-after flavors in foods, and for good reason – it pleasurably stimulates our taste receptors. But what if we told you that all that sweetness isn’t so sweet after all? In fact, consuming large quantities of sugar can have some pretty nasty consequences for your health. Keep reading to find out more.


Despite marketing claims, there really isn’t a “healthy” sugar or sugar alternative. Sugar in the body regardless of form, all is broken down into simple sugars. In fact, the body does not differentiate between naturally occurring sugars and those that are added to foods.  The metabolism pathway is the same regardless of whether sugars are naturally occurring or are added to foods during processing. It does not matter whether the sugar is of natural origin or whether it is added, all sugars are broken down into glucose, fructose and galactose. These three simple sugars are absorbed into the blood stream where they are used by the body for energy or stored as glycogen in muscles or fat cells.


The glycemic index (GI) is a numerical system for measuring the effects of carbohydrates on blood glucose levels. Carbs are ranked according to how they affect blood sugar. Foods that contain simple sugars, such as white bread and soda, have high GI scores because they cause sudden spikes in blood sugar. Foods that contain complex carbs, such as oatmeal and legumes, have low GI scores because they cause gradual increases in blood sugar.

The glycemic index is a complicated system for determining the speed at which carbohydrates digest and reach the bloodstream as glucose. However, it does not take into account how much of those carbohydrates one actually consumes or what the total effect on blood sugar levels will be.

For example, the glycemic index of table sugar is 65 compared to carrots which have a glycemic index of 49. However, one teaspoon of table sugar only has 4 grams of carbohydrates- about the same amount as one medium carrot. It would take 18 carrots to provide 16 grams of carbohydrate, which is equivalent to one teaspoon of table sugar.

The glycemic load (GL) is the best way to measure how fast carbohydrates are likely to raise your blood sugar levels after eating them.  It takes into account both the GI number and the actual amount of carbohydrate consumed. For example, table sugar has a high glycemic index (65), but a low glycemic load (4) (carrots have a high glycemic index, but a very low glycemic load).


Refined sugars are all made up of the same thing: sucrose. No matter what type of sugar you choose, if it is not listed as “sucrose” or another specific type of sugar, then it is most likely made up of mostly table sugar.

The best way to avoid hidden sugars in foods you eat is to look for ingredients that end in “-ose”. These are all different types of simple sugars: glucose, maltose lactose, sucrose, fructose, galactose, xylose.


Sugars provide fewer calories per gram than fat and protein. For example, one teaspoon of sugar contains 16 grams of carbohydrate and 4 calories; one tablespoon of honey contains 64 grams of carbohydrate and 265 calories; and one pat of butter contains 0 grams of carbohydrate and 509 calories. The high calorie content in sugars is why people gain weight when using them.

Added sugars are different from naturally occurring sugars, such as the lactose found in milk or fructose in fruit, which also contain other nutrients. Added sugar is just that — added to foods during processing where it provides calories but no other nutritional value.


Maple Syrup: Maple syrup is one of our top ranked sugars because of the minerals such as manganese zinc, and iron, and is also a good source of antioxidant plant nutrients. Maple syrup is also on our top ranked lists as it is a more sustainable sugar. Maple syrup is sourced from the sap of maple trees; tapping the trees doesn’t harm the tree or affect future yields.

Date Sugar: Date syrup is not just sugar as it is actually a food made from a fruit.  Dates are one of the richest sources of antioxidants, specifically phenols. Date sugar is also gluten-free and contains 3 grams of fiber per teaspoon for “bulk” so you can use less sugar in recipes. 

Raw Honey:  Honey is an antioxidant powerhouse.  Raw honey contains more antioxidants than most other sweeteners because of its darker color, which comes from the plant phytonutrients that bees collect from dark-colored flowers. I prefer pure raw honey over “raw” blends with added sugars or flavors.

Blackstrap Molasses:  Molasses are by-products of the process to make sugar white.  Blackstrap is the final product, which makes it the most concentrated in nutrients, including calcium potassium, iron, magnesium and vitamins B6 and B12.

Raw Cane Sugar:  Raw cane sugar has a milder flavor than refined white and brown sugars and can be used as a replacement for either in cooking and baking. Despite the title, it is actually not a raw sugar.  The crystals are made from evaporated sugar cane juice which can be unrefined, but is often further processed via filtration and decolorizing. Raw cane sugars are also found under the names of turbinado, panela, demerara and muscovado.


There are also no calorie sweeteners that have no calories and no impact on blood sugar. However, there is a downside to this.  No calorie sweeteners don’t provide any nutrients and actually could potentially cause increased cravings for sweet foods because the body expects calories when it senses a sweet taste. Also, no calorie sweeteners may not be safe to consume long term. Most health organizations recommend eating these products in moderation. Sugar alternatives are highly processed and many may cause inflammation and other health problems; they also deplete the body of minerals and nutrients.

Stevia:  Stevia is a plant that has been used as a sweetener for hundreds of years. It contains no calories because it doesn’t break down during digestion, so all you absorb is its sweetness. I recommend getting your stevia from the whole plant rather than a refined product and I prefer liquid or powdered forms to granulated.

Monk fruit:  Monk fruit is another natural, no calorie sweetener that has been used for hundreds of years in China and Southeast Asia. It contains antioxidants and has been used as both medicine and tea to aid digestion. Refined products contain some calories as they must be concentrated from the fruit.

Yacón Root: Yacón root is a plant native to South America and has been used as food and medicine for centuries. It contains inulin which helps make it taste sweet and provides prebiotics, like dietary fiber, that feed the health promoting bacteria in our gut.

Allulose:   Allulose is a naturally occurring sugar that is very rare. It tastes sweet but doesn’t raise blood sugar or insulin levels, which has made it popular with makers of reduced calorie foods. We don’t know enough about allulose because it hasn’t been studied long term so we are unsure as to if it can cause problems when consumed regularly.

So, what’s the takeaway? The bitter truth is that all of those lovely sweeteners we love are metabolized in the same way, and can have negative effects on our health when overconsumed. While sugar intake has been linked to obesity and type II diabetes, it may also play a role in other chronic diseases. Next week, we will explore the impact on sugar and healthspan. In the meantime, follow us on social media for weekly insights in the field of longevity.

Maryland Functional Medicine

Maryland Functional Doctor

As we approach the end of another year, many of us are looking ahead to the New Year and setting resolutions or intentions for ourselves. One area that is ripe for change is our health. One great way to set healthy intentions for the New Year is by thinking about what you want to achieve physically, emotionally, and mentally. Maybe you want to lose weight, get in shape, or eat healthier. Perhaps you’d like to reduce stress levels or boost your energy. Here are some tips for setting effective health intentions for the New Year.

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In medicine, we work daily with our patients and set goals we want them to achieve by their next follow-up visit. Setting these realistic goals allow for them to not only be an active participant in their health, but to create daily habits to achieve their optimal level of wellness. Similarly, you can set goals for yourself. Not only can setting health goals help you achieve your objectives, but they can also be a great source of motivation as well as encouragement as you work towards those goals on a daily basis.


First, you want to identify what it is that you want to change about your health.

Are you experiencing symptoms or do you want to prevent symptoms?

Are you feeling stressed out by the daily grind of life, are you not sleeping well at night, are you looking for an alternative way to manage symptoms of depression?

Do you feel like this is a good time in your life to achieve one of these objectives?

Once you have identified the things that you want to change, it is important to realize that change is a process and nothing will happen overnight. Remembering this can give you the motivation to push through those times when your progress is not as quick as you would like.


Once you’ve set realistic goals for your health, create small daily habits that can help you achieve your health objectives. For example, if your goal is to lose weight, schedule time each day for exercise and track your food intake. If sleep deprivation is affecting your mood or productivity at work, try to go to bed earlier or take a 20-minute nap during the day so you are more alert.

If you are struggling to stay motivated on your new behaviors, set up some accountability for yourself. For example, if you are trying to lose weight, tell a friend about your goals and ask him or her to check in with you daily on your progress.

Lastly, remember that achieving health goals is not only about the big picture of your overall well-being, but also the little things that we do each and every day. By committing to a health change and creating daily habits that can help you maintain this new behavior, you will be on your way to a happier and healthier 2022!


Fad diets are common in the new year.  Many of these diets can help you lose weight quickly, but it is typically not sustainable and they provide no long-term benefits.

Eating healthy does not mean that you have to go on a strict diet or eat bland food. It simply means that the majority of your foods each day should be fresh fruits and vegetables, whole grains (e.g. brown rice or quinoa), lean proteins (e.g. fish, poultry, beans), and healthy fats (e.g. nuts, seeds, olive oil). While you can lose weight on these diets, they are not good for the body long-term since they do not include many of these important foods that contain antioxidants and other important nutrients that help us function optimally.


Many times, when we don’t get enough sleep, we find ourselves reaching for a cup of coffee in the morning to wake up our brains and bodies. Or perhaps you have noticed that after a night without much sleep, your mood is less than stellar and you cannot concentrate as well at work.

While sleep is not the only factor in maintaining good moods or optimal energy levels, it plays an important role.  Make sure that you are getting 7-9 hours of sleep each night to maintain your health and wellness!


Studies indicate that participating in regular exercise helps prevent dementia, Alzheimer’s disease, and mild cognitive impairment. Regular exercise also has benefits for body weight, cardiovascular health, sleep quality, productivity at work, mood disorders (e.g., anxiety and depression), stress management, self-esteem and self-confidence, and the list goes on.

If you are not currently exercising regularly, start by committing to exercising 3-4 times per week for 30 minutes each time.  Remember to always speak with your physician before starting any exercise program!

It is also important to note that exercising does not have to be boring or strenuous. Find activities that you enjoy, such as walking, hiking, swimming, biking, yoga or dancing. And if you love a good workout in the gym, make sure you are getting results from all of your hard work!


– Map out your goal and the steps it will take to achieve this goal.  Be specific and realistic when you set your health optimization goals so that you can identify what is needed to reach your objective.

– Determine the resources available in order to meet these goals, such as time, money, family support, etc.

– Identify a support system of friends and family who are trying to achieve positive health changes as well. Having this network of people around you will help you stay accountable on your path to optimal health!

– Stay focused and dedicated to these new behaviors by reminding yourself why you made these goals in the first place.  Revisit your goal statement often, whether it is printed out and hanging near your computer or written on a notecard in your wallet. Having this daily reminder of why you are taking these steps to improve your health will help motivate you throughout the year and beyond!

– Track your progress and celebrate each success along the way. This does not mean that you need to weigh yourself every day, but rather take note of how you are feeling and how it is easier to stick with your new behaviors.

Health optimization is not an easy task, but by setting your intentions for 2022 now, you are preparing yourself to achieve these goals. So say goodbye to those FAD diets that promise quick weight loss or guilt-free eating habits that leave you feeling deprived. Instead, commit to making healthy lifestyle changes that will improve your health and wellness in the long term and make sure your friends and family are on board with keeping you accountable!

I hope that this article was helpful to you and wish you a very happy, healthy 2022.

Maryland Functional Medicine 

DNA methylation is a biological process that changes the structure of DNA. It can affect how tightly your genes are packaged and how easily they’re turned on or off. This process is an important part of normal cellular activity and helps protect cells from damage caused by stressors like toxins, poor diet, etc. Follow us on this week’s post to understand more about this process and its role in human health and longevity.

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Methylation is the addition of a methyl group (-CH3) to a molecule. In the context of DNA, it’s the addition of a methyl group to one of the bases, cytosine (C). DNA is formed by two strands that form a helical structure (also called the double helix). Each strand is comprised of nucleotide bases, which are labeled A, T, C, and G.[i] There are four types of DNA methylation:

1.  5-methylcytosine:  This is the most abundant and stable type of cytosine methylation.[ii]

2.  5-hydroxymethylcytosine: This is a byproduct of active DNA demethylation and can be reformed into cytosine methylation.

3. 6-methyladenine:  This is found in bacterial DNA and is a result of the methylation of adenine.

4. N6-methyladenine: This is also found in bacterial DNA and is the result of methylation of adenine, but it’s a result of a different enzyme system.

The addition of a methyl group to cytosine alters the way the DNA is packaged and can affect how genes are expressed. Methylated DNA is less accessible to proteins that read DNA ( transcription factors) and can lead to  gene silencing.

Silencing this process can change how genes are expressed. The methylated DNA is said to be “methylated” and the unmethylated DNA is said to be “unmethylated.” More than 70% of human CpG islands (sequences on chromosomes) are methylated.


When genes contain methyl groups, they tend to remain inactive and gene expression is decreased.  This is because methylation helps to “wrap” the DNA around proteins called histones, which keeps them from being accessed by transcription factors. Transcription factors refer to a group of proteins that bind to the DNA and help turn genes on or off.

Even though methylation can decrease gene activity, this process is important for normal cellular functioning. For example, it helps control inflammation by turning off genes that promote inflammation. It also helps turn off tumor suppressor genes in cells that don’t need to divide – like heart or nerve cells.

That being said, when it’s dysregulated, improper methylation has been linked with a variety of diseases, including cancer, Alzheimer’s disease, and autism.

The addition of a methyl group can also change the physical shape of the DNA molecule, making it harder for transcription factors to bind to it.

On the other hand, when genes are unmethylated, they tend to be turned on and gene expression is increased. When genes lack these methyl groups, the proteins they encode are more likely to be produced. This is why methylation can affect things like cancer development, as well as normal cell function.


DNA methylation is a necessary part of normal cellular function because it protects against stressors that can damage DNA. Cells are constantly under attack from harmful substances, radiation, toxins, poor diet, etc., so they have to be able to protect themselves. DNA methylation helps to do this by silencing genes that could cause damage.

When the body is healthy, DNA methylation works properly and everything runs smoothly. However, when the body is not healthy, it can lead to problems with methylation. For example, when a person is stressed out or has a poor diet, their cells become stressed and DNA methylation decreases.


What causes improper methylation in the body?

There are a few things that can cause problems with methylation, including:

  • Nutritional deficiencies: A person who is deficient in certain vitamins and minerals (like B6, B12, zinc, and magnesium) may have problems with methylation.
  • Environmental toxins: Toxins from the environment can also interfere with methylation. These toxins include things like pesticides, herbicides, plastics, and heavy metals.
  • Inflammation: When the body is under chronic stress or has high levels of inflammation, it can have trouble with methylation. This is because high levels of free radicals can damage DNA and lead to problems with methylation. Methyl groups also help protect cells from free radical damage.
  • Age: As we get older, our ability to methylate decreases. This is because as we age, we lose cells that help with methylation, and our DNA becomes more susceptible to damage.[iii]
  • Genetics: Some people are born with genes that make it harder for them to methylate DNA properly.


While there is much to be discovered on DNA Methylation and longevity, there are some early indications that it may be involved in the aging process[iv]. One study showed that people with high levels of methylated DNA lived longer than those with low levels of methylated DNA. Another study showed that when cells are unable to methylate DNA, they age more quickly. More research is needed to determine the role of DNA methylation in longevity, but these early findings suggest that it may be important.


DNA methylation is a complex process that plays an important role in normal cellular function. When it’s properly methylated, it helps to protect against environmental stressors and inflammation. It also plays an essential role in mitochondrial function, which is important for energy production.

However, when the body becomes stressed – whether it’s because of deficiencies, toxins, inflammation, age, genetics, or other factors – then DNA methylation can become impaired.  This can lead to a variety of problems, including cancer, neurodegenerative diseases, and other health issues.  It’s important to understand how it affects you and what changes can be made for optimal health. We hope this article has helped shed some light on what DNA methylation is and how it works in your body. Follow us next week!

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.





Oxidative stress is a term that refers to the deterioration of our cells and tissues due to an imbalance between the production of free radicals and antioxidants. Free radicals are highly reactive molecules with unpaired electrons, which can cause harm when they interact with other important molecules in our cells. Antioxidants, on the other hand, work by donating their extra electron to neutralize free radicals before they can do any damage. This balance between free radical production and antioxidant protection is essential for health because it has been shown that oxidative stress plays a role in many chronic diseases such as cancer, diabetes mellitus type 2, cardiovascular disease (CVD), Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), and more. There are many risk factors for oxidative stress including genetics, diet, exercise habits and environmental pollution. In this blog post we will be discussing what oxidative stress is, how it affects our body, and more!

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Oxidative stress is a natural phenomenon that occurs through metabolic processes in the body. It’s made by the release of free radicals during the process of lipid peroxidation, which involves an enzyme called lipoxygenase producing ROS while breaking down fats under oxidative conditions.[i] In other words, oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the body’s ability to protect itself with antioxidants. Reactive oxygen species refers to oxygen molecules that have unpaired electrons, making them “reactive”. ROS is made when oxygen interacts with other compounds; this can be caused by many external factors such as air pollution or cigarette smoke. When the produced ROS exceeds the body’s protection (antioxidants), it causes the oxidation of important molecules like DNA, proteins, and lipids (fats). These ROS include free radicals such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, which form during normal metabolic processes. Superoxide anions refer to the combination of two oxygen molecules to form a free radical. This compound lacks an electron and can damage different types of biomolecules such as DNA, proteins, and lipids through oxidation. Hydrogen peroxide is made when superoxide anions break apart and are known as the primary toxic molecule of ROS. Hydrogen peroxide can also damage DNA, proteins, and lipids by oxidizing them. The hydroxyl radical is formed when hydrogen peroxide reacts with the superoxide ion, producing highly reactive OH-radicals that break down cell membranes and tissues in the body.

The release of these free radicals increases when there is damage to mitochondria in our cells, which is crucial for producing energy. Mitochondria (the part of our cells that turns food into energy) has to work harder during oxidative stress and requires large amounts of antioxidants.[ii]


Because oxidative stress involves the production of free radicals, it can damage many types of molecules in our cells such as lipids (fats) and DNA. This is important because cell membranes and DNA are largely made up of lipids and contain genetic information that tells our body how to function. A study found that when there is an imbalance between ROS and antioxidants, it can cause oxidative damage to lipids in our cells. This is important because lipids are the fatty molecules that form cell membranes and protect our cells from foreign objects. When lipid peroxidation occurs, free radicals attack the lipids in cell membranes damaging them. When the cell membrane becomes damaged, it increases permeability which allows molecules to leak into the cell causing further damage to proteins and other important molecules. Free radicals can also directly cause oxidative stress through DNA damage. [iii]This occurs when free radicals combine with oxygen in essential parts of our DNA such as the mitochondrial genome, which is crucial for producing energy within cells. The combination of these oxidative damages creates a domino effect throughout our body cells. Damage to DNA results in the inability of cells to divide properly, which leads to uncontrolled cell growth. This can cause tumors and cancerous tumor cells to form all over our bodies. Damages caused by oxidative stress on lipids (fats) is important because fats are part of the lipid bilayer that forms the outer membrane of every living cell. When the lipid bilayer is damaged by ROS it leads to improper functioning in cells throughout our body.

When our body is under oxidative stress, there’s an accumulation of free radicals in our cells which results in damages to molecules like lipids (fats) and DNA. This can cause many problems in different parts of the body including:

– Increased atherosclerosis, is where plaque build-ups form in arteries causing them to harden.

– Increased risk for developing cancer and tumors because of DNA damage caused by ROS.

– Damages to cell membranes that lead to improper functioning in cells throughout our body.


Oxidative stress can be caused by many factors including environmental pollutants such as cigarette smoke, ultraviolet (UV) radiation from the Sun, and chronic infections like hepatitis. There are several other common sources of oxidative stress including:

– Smoking tobacco

– Eating high-calorie meals that contain a lot of fat, which can lead to obesity and increase the risk for cardiovascular disease.

– Consuming caffeine or alcohol in excess, because these substances inhibit enzymes that produce antioxidants in our body.

– Consuming a poor diet which may lack the necessary vitamins and minerals needed to make antioxidants in our body.

– Living a sedentary lifestyle, because can lead to weight gain that results in cardiovascular disease.

– Exposure to pollutants, which can come from the workplace or even the local environment.

One of the biggest sources of oxidative stress is exposure to sunlight. [iv]UV radiation that comes from sunlight has many harmful effects on our body including skin cancer because it promotes free radical formation in our bodies. When we are exposed to UV radiation it causes oxidation reactions in the skin, which damage proteins like collagen. Collagen is what gives our skin its strength and elasticity. When it becomes damaged, these effects lead to wrinkles and sagging in our skin.

Oxidative stress is a term that refers to the deterioration of our cells and tissues due to an imbalance between the production of free radicals and antioxidants. But what does this have to do with longevity?  Studies show that people who experience high levels of oxidative stress during their lifetimes may be at greater risk for developing dementia or other age-related diseases later on in life. There are many ways in which we can help reduce oxidative stress, such as with antioxidant rich foods. What are some easy ways you have increased your antioxidant intake lately? Share with us in the comments below or follow us on next week’s blog for more information related to oxidative stress and longevity.





Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

Maryland Functional Medicine 

Maryland Functional Physician

Maryland Functional Doctor

Mitophagy is a process that occurs in cells, and it’s essentially the destruction of old or dysfunctional mitochondria. It’s important to know about mitophagy because as we age, our bodies lose their ability to carry out this process properly. When mitophagy does not occur properly it can lead to mitochondrial disease which has been linked to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. This blog post will provide an overview of what mitophagy is and why it matters.

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The word ‘mitophagy’ was coined in 2007 by the researchers who discovered this process. The prefix mit- means thread and phage means eat, so we define mitophagy as the destruction of mitochondria via a cellular mechanism called autophagy. Autophagy is a process that involves the degradation and recycling of cellular components. Mitophagy is the selective kind of autophagy mechanism that removes mitochondria.  A cell can digest its own organelles through this process, but it will only remove damaged structures and not healthy structures. This selective quality is what makes mitophagy so unique because most other forms of autophagy just degrade cellular components indiscriminately.

There are two other forms of autophagy: chaperone-mediated autophagy and micropexophagy. [i]

  1. Chaperone-mediated autophagy is a process that degrades damaged proteins and this type of degradation occurs in the lysosome or sac like structure.
  2. Micropexophagy on the other hand targets  mitochondria for degradation.


The mitochondria is an organelle that is responsible for converting energy into a form of molecules that our cells can use.[ii] Inside the mitochondria are enzymes called electron transport chains (ETCs) which take electrons and try to pair them with hydrogen atoms to produce chemical energy. This process also creates free radicals as by products, so our cells must have an enzyme called superoxide. Superoxide dismutase (SOD) eliminates superoxides and turns them into hydrogen peroxide. Hydrogen peroxide (H2O2) is broken down by catalase and glutathione peroxidase into water and oxygen gas.

This cellular structure is responsible for helping generate ATP (Adenosine triphosphate) which stores energy in the form of phosphate bonds. Cells need ATP to get rid of excess calcium ions that build up due to metabolism, and also to open up calcium ion channels for muscle contraction. Severing of the mitochondria from the rest of a cell triggers apoptosis, which is a programmed form of cellular death. The lack of a link to other organelles and its proximity to calcium ions makes it susceptible to damage. Because of this susceptibility, cells have developed a mechanism which allows them to dispose of defective mitochondria.


Mitophagy is a type of autophagy and there are three steps that must occur for this mechanism to carry out successfully:[iii]

1. The first step is the creation of an isolation membrane which surrounds the mitochondria, so the rest of the cellular components aren’t degraded.

2. The isolation membrane which elicits the form of selective degradation known as mitophagy is created by a multi-protein complex called PINK1 and Parkin.

3. The last step involves the elimination of the mitochondrion through fusion with lysosomes (the cellular structure responsible for degrading other organelles) via a double membrane structure called an autophagosome.


There are two types of mitophagy that exist: Macro-autophagy and Micro-autophagy.

Macroautophagy begins with the formation of an isolation membrane around the mitochondria from a multi-protein complex composed of several proteins such as Nix, Parkin, AIFm2 and FUNDC1.

This isolation membrane then fuses with a lysosome which creates an autophagosome. The autophagosomes carry the mitochondria to the cytoplasm for degradation into amino acids, fatty acids, and nucleotides.

Microautophagy is a process that creates a small isolation membrane around the mitochondria from a single protein called Ulk1. This process is often used in response to stress, but there hasn’t been direct evidence of this process occurring in mammalian cells.


A protein complex called PINK1-Parkin is believed to be the primary regulator of mitophagy.  This complex is required for creating the isolation membrane that leads to mitophagy.

PINK1 has been found to regulate this process by promoting mitochondrial fission, imparting an isolation membrane around the mitochondria, and recruiting Parkin which becomes phosphorylated in response. When PINK1 is degraded or loses function through mutations, it can lead to PINK1-associated Parkinson’s disease.

Parkin is also required for mitophagy, and it acts in a parallel pathway to that of the PINK1-Parkin complex by creating an isolation membrane around mitochondria through phosphorylation of proteins involved in fission which leads to the formation of an autophagosome.

This suggests that PINK1-Parkin play a major role in the regulation of mitophagy.


Mitophagy is often found to be defective in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease[iv]. This is because faulty mitochondria are not properly eliminated, leading to cellular damage.

Since mitophagy is important in neuronal function, it follows that this process would be affected in cancer disorders. Cancer cells often have uncontrolled mitochondrial biogenesis, and this leads to extreme energy demands in cancerous cells which can be exploited. Mitochondrial biogenesis refers to the creation of new mitochondria from the division of existing ones.[v] This process is regulated by a protein complex that includes PGC1α and NRF1, which are often over-activated in tumor cells.

Cancer cells also need the ability to oxygenate themselves, so putting selective pressure on these cells through drugs that inhibit mitochondrial function can lead to their death. Inhibiting mitophagy could potentially decrease the effectiveness of such chemotherapy treatments, however research has shown that some chemotherapy drugs stimulate mitophagy so it may still have some use.

In addition, mitophagy is important for cardiovascular function and the development of stem cells. Mitochondrial biogenesis is a crucial process for stem cell formation and differentiation into progenitor cells. Mitophagy also ensures that damaged mitochondria are eliminated in cardiovascular cells.

Mitophagy is important to our longevity and healthspan because it allows the removal of faulty mitochondria that could potentially lead to cell death. Cell death leads to the death of the organism, so this process is critical for cellular health. Maintaining optimal cellular health is a key component in healthy aging, and efficient mitophagy is necessary for elimination of damaged mitochondria. We would love to see you next week on another blog post – Tune in then!

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.






Fisetin is a flavonoid found in many fruits and vegetables. It has been shown to have anti-inflammatory, antioxidant, and anticancer effects. Because of the potential health benefits it may provide, fisetin supplements are becoming more popular as people look for alternatives to other medications that they may not be comfortable with or want to take long term.  In this blog post we will explore what fisetin is, why people are taking it, potential benefits and discuss current research being done around Fisetin and how this could impact future treatments available for those looking to improve their health naturally.

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Origins & History of Fisetin

Fisetin is a naturally occurring flavonoid compound. Flavanoids are water-soluble compounds found in plants and have antioxidant properties. Water-soluble means that Fisetin can dissolve in water. Fisetin is not found to be fat-soluble, which means it cannot dissolve into fats or lipids that are normally soluble in oils. Fisetin was isolated from the Fruiting bodies of a Fungus called Fomes Fomentarius. The Fruiting body of this fungus is responsible for producing all of the spores that are used to reproduce. Fisetin can also be found in many plants including Ginko Biloba, strawberries, persimmons. Fisetin’s chemical structure was first identified chemical formula was first described by Austrian chemist Josef Herzig in 1891. Fisetin can be found throughout the plant kingdom, where it acts as a photosynthesis inhibitor and UV protectant. Fisetin has even been isolated from insects, including ants, aphids, and wasps.

Fisetin is also said to be one of the many flavonoids that are found abundantly in the plant subfamily Cornoideae, which includes Foeniculum vulgare, Foeniculum dulce, and Coriandrum sativum. Fisetin was first isolated from Foeniculum vulgare, Fennel. Fisetin was first isolated from the bark of the Pacific wax myrtle tree and has since been found in many fruits and vegetables. Fruits and vegetables that are high in fisetin include:

– Strawberries; specifically, they are Fisetin’s highest food source.

– Red grapes

– Apples

– Asian pear

– Fennel seeds  (Foeniculum vulgare) Fisetin is a member of the flavonoids, which are plant pigments produced by many plants to help protect themselves from outside stressors, such as ultraviolet light, insects, and herbivores.

Why are people taking Fisetin?

Natural supplements are becoming increasingly popular in the health and wellness community. There are a number of different types of natural supplements such as probiotics, prebiotics, digestive enzymes, amino acids and herbal extracts that all serve their own specific purposes. There are many reasons why people take natural supplements. Some people want to support their bodies’ natural processes, others want natural help with a specific health concern, and some just want to maintain good health. Dietary supplements have been one way that consumers have sought to fulfill unmet dietary needs. Fisetin is one of many supplements like this that people are turning to attempt to make themselves feel better. Many of my patients opt to take supplements to make sure they get enough essential nutrients and to maintain or improve their health.


Fisetin is a naturally occurring antioxidant found in many fruits and vegetables. Fisetin is known as a neuroprotective agent, meaning it has been shown to have potential benefits in helping the body fight against both acute and chronic neurological diseases.  Fisetin is one of the most common and bioactive flavonoids which possesses potential neuroprotective effects. Fisetin also enhances learning and memory, decreases neuronal cell death, and suppresses oxidative stress.  Fisetin has been shown to have significant protective effects on the body from oxidative stress, which is why Fisetin may be taking it as it can potentially be beneficial for those looking to improve their health or prevent disease. Oxidative stress refers to the level of damage done to cells in the body by free radicals. Fisetin has been shown to have some effect against oxidative stress, but it is not yet known whether Fisetin itself can actually reduce oxidative stress or if Fisetin can enhance antioxidants that are already present in the body. It is also unknown how Fisetin works as an antioxidant. Fisetin may work as a scavenger, Fisetin can bind to free radicals, Fisetin could be regenerating the antioxidants that it is acting with, or Fisetin itself may act as an antioxidant. There is still much to learn about Fisetin.


As we age, we accumulate damaged cells. Damaged cells can cause tissues to function improperly or not work at all. Fisetin has been shown to reduce senescent cell burden in mice by activating the body’s enzymes that clear out senescent cells. Senescent cells are cells that have stopped dividing to replicate themselves. Senescent cells can accumulate in all tissues with age and secrete pro-inflammatory cytokines and chemokines. Fisetin has been shown to increase the lifespan of mice. In a recent study, Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.


mTOR is responsible for controlling cell growth, division, and metabolism. Recent research shows how Fisetin inhibits the mTOR pathway. When you inhibit the mTOR pathway you are essentially slowing down the aging process.

Fisetin & Inflammaging

Inflammaging refers to the chronic low-grade inflammation that is caused by cellular damage, oxidative stress, and mitochondrial dysfunction. Fisetin is believed to be able to reduce inflammation because Fisetin has shown an ability to reduce cellular (nuclear) damage in animal studies. This is accomplished by Fisetin’s ability to inhibit by inhibiting pro-inflammatory enzymes and substances, like lipoxygenases and NF-kB.


As research continues on this compound more information about how fisetin could be used for medicinal purposes will be revealed. Fisetin holds great potential for multiple applications in medicine, and research studies have shown Fisetin’s positive anti-inflammatory and anticancer effects on different cell types. Over the last two decades, much attention has been drawn to plant-derived bioactive compounds as novel therapeutic agents for treatment of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The current research suggests that the benefits of Fisetin may be worth considering for those looking for natural options to improve their health.

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

The extracellular matrix is a network of proteins and other molecules in the space between cells. It helps cells attach to one another and move around. You can think about this like scaffolding for building a house: it provides support and structure for all kinds of activities inside the cell without getting too involved in how those things happen. When there’s damage or injury, it also sends signals to help repair or replace damaged parts of tissue by recruiting stem cells from elsewhere in the body. In this blog post, we will explore how extracellular matrix regulation works to maintain homeostasis from birth to death so you can better understand your body’s natural aging process!


The extracellular matrix (ECM) is a dynamic structure that provides a structural framework for cellular organization and movement. It is a three-dimensional space, extending between cells that are defined by components produced by the cells themselves as well as cells that they neighbor.

The ECM consists of a dynamic mixture of structural proteins which are typically secreted from the cell into the extracellular environment. The extracellular matrix is made up of many components, including molecules like collagen and elastin, macromolecules like glycoproteins or proteoglycans, proteins like adhesion proteins that allow cells to bind to each other, growth factors that signal new tissue formation, and others.

Collagen is one of the most prominent components of the extracellular matrix. It provides strength and stability to tissues and is primarily responsible for wound healing and tissue repair.

There are many types of glycoproteins, or proteoglycans, which give the matrix its winding appearance, similar to DNA’s iconic double helix. These macromolecules allow cells to recognize and bind to the matrix components.

Several types of adhesive proteins promote cell-to-cell contact, which can be found on either side of a plasma membrane where they’ll spread out from the cell’s surface towards the extracellular matrix. These proteins will crosslink, or bond together with other adhesive proteins to form a mesh that reinforces the adhesive bond between cells.

4 Major Purposes of the Extracellular Matrix:

Containment of cell growth: This refers to how the matrix can “wrap” around cells while still allowing them to grow in size while confined by the surrounding ECM.

Cell signaling and communication: Cell signaling and communication refer to how cells can send signals through the matrix so that growth and development happen in the right place at the right time.

Binding cells together to form tissues or organs:  The adhesion proteins that hold cells together can also link them to the extracellular matrix.

Removal of dead or damaged cells from the body:  Cells are constantly dying and being replaced, so the ECM will send signals to attract stem cells that can migrate towards their location within tissue in order to repair or replace damaged cells.


The extracellular matrix is a critical mediator of cell behavior. In fact, cells respond to their environment by changing shape and altering gene expression in order to perform their job properly. 

Cell adhesion: This refers to how cells bind together very tightly with adhesive proteins that can crosslink with other adhesive proteins across the plasma membrane so they strengthen the bond between cells.

In order for cells to join together correctly at the right times and places, they need to be able to sense their environment and respond by sending signals through a network of proteins that bind together in a very specific way. So if a developing embryo is going to form into multiple layers that will eventually become distinct tissues or organs, cells in each layer will need to bind to the ECM and pass signals through it to be able to change shape and function into whatever they’re supposed to become.

3 Types of Cell Adhesion:

Integrin: These proteins anchor cells to the extracellular matrix, primarily binding between adhesive proteins on one side of a plasma membrane and “integrin-binding sites” on the other side of the plasma membrane.

Cell-matrix adhesion: This refers to how cells can bind directly to ECM components, which involves integrins as well as other types of adhesion proteins.

Compartmentalization/Segregation: This refers to how cells can create closed boundaries that will separate different tissues from each other.

In order for cells to be able to create compartments, they need to regulate the way substances enter and exit the local environment. In fact, many types of tissue have a limited list of molecules that can diffuse across their borders in one direction or another – this is called “selective permeability”, and it’s a feature of many cell types.

2 Main Features of Selective Permeability:

1) Pores in the plasma membrane allow solutes to move through them but prevent water from moving freely through those pores, due to the presence of lipid bilayers. This allows cells to selectively control which molecules can enter or exit their local environment.

2) Cells can have a different level of permeability in different directions, so some proteins will move freely across the cell membrane while others cannot – this is called “anisotropy”.


Different types of cells can adjust how permeable their plasma membranes are to help create local boundaries and also take in the right molecular nutrients for their job. In regards to the extracellular matrix, the ECM can bind to integrins on the plasma membrane of cells, which helps create a boundary that separates tissues from each other. Integrins are the major cell adhesion proteins, which means they bind cells to the ECM. Cells will be able to pass molecules through the border into neighboring tissues, but if the molecule is too large it won’t fit through the pores of the membranes and therefore cannot go across. All cells have distinct levels of permeability in different directions to help create a very specific environment for each cell type.


Part of what allows cells to remain differentiated is the extracellular matrix. It provides cells with the appropriate molecular signals to maintain their state, and when they move to a different tissue it also helps ensure that they will behave correctly in their new local environment – which is why this system breaks down when there is damage or disease. Abnormalities in the extracellular matrix are linked with age-related diseases. When ECM is broken down, it releases many different molecules that can cause inflammation. Inflammation is an immune response meant to eliminate threats to the body, but chronic inflammation can be very harmful and eventually result in death. When this happens over time the extracellular matrix will degrade and build up in ways that are detrimental to our health. When this happens, it causes “inflamm-aging” which is when inflammation builds up over time due to wear and tear on the body.

As we age, the extracellular matrix continues to degrade in many ways. The aging process involves many deleterious changes in the cells and tissues of an organism, which can affect how it functions. Lifestyle factors may accelerate the degradation of the extracellular matrix. Since ECM is responsible for cellular differentiation, preventing this degradation could lead to greater longevity because it would allow cells to maintain their state and continue functioning properly.  

Disclaimer: The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Additionally, the information provided in this blog, including but not limited to, text, graphics, images, and other material contained on this website, or in any linked materials, including but not limited to, text, graphics, images are not intended and should not be construed as medical advice and are for informational purposes only and should not be construed as medical advice. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Before taking any medications, over-the-counter drugs, supplements or herbs, consult a physician for a thorough evaluation. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this or any website.

The body’s immune system is a complicated, elegant machine that protects us from the outside world. It does this by recognizing invaders through amazing sensing mechanisms and responding to them with incredible precision. In the case of cell danger response (CDR), our cells do their best to protect themselves as they are being attacked by viruses or bacteria. Yet CDR can be dangerous if it overreacts and causes inflammation – which can lead to chronic diseases such as diabetes or even cancer. In this week’s blog post we will not only explain what CDR is but also how we minimize its risks so we may live a healthy life.


The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. 

How it works is by the cell senses that it is being attacked, then using specialized proteins to monitor our metabolism. When CDR is activated, the body will use available energy sources and switch its focus to self-defense rather than growth and reproduction. CDR is a mechanism that allows cells to sense ‘danger’ that may be caused by viruses or bacteria. This danger can also come in the form of molecules such as DNA, RNA, and proteins – all of which are components found inside our cells.  When these substances get leaked into the extracellular environment, CDR kicks into gear.

The activated CDR will then enter into a cascade – this is where it gets its name, the danger response cascade (DRC). The danger response cascade can be broken up into five steps that occur in succession: 

1. Detection: Detection of PAMPs (e.g., pathogen-associated molecular patterns like lipopolysaccharides) or damage-associated molecular patterns (DAMPs). PAMPs are substances that can be recognized by specialized receptors, such as Toll-like receptor (TLR), NOD-like receptor (NLR), and RIG-I like helicases (RLH). DAMPs refer to the cellular debris or damage that results from being attacked. 

2. Activation of MAPKs, IKKɛ, TBK1, PKA, and PKR. Next these activated enzymes activate transcription factors (which refers to a biochemical process by which a particular gene’s instructions are copied into RNA) that then activate or suppress inflammation-promoting genes while suppressing other essential genes involved in repair pathways. When we discuss activated enzymes, this refers to enzymes that have been phosphorylated, which means a phosphate group has been added to the enzyme.  

3. Activation of transcription factors such as NF-kB, FOXO3a, and HIF1α. These transcription factors then go on to stimulate or suppress the transcription of genes that regulate inflammation and also cell survival. 

4. Activation of MDA5 & RIG-I: MDA5 and RIG-I are critical to the CDR response because they activate an antiviral pathway known as type I interferon production. Type I interferon production is a pathway that allows our body’s immune system to help fight infections. 

5. Secretion of inflammatory cytokines to induce downstream immune cells to take action against the infection. Inflammatory cytokines are a group of signaling proteins that trigger inflammation at sites of infection. The cells which release these cytokines are called antigen-presenting cells (APCs) and include monocytes, macrophages, dendritic cells, and B lymphocytes. This cascade is what allows CDR to induce inflammation – yet it can have negative consequences if activated over and over again.

In addition, CDR can also occur in response to non-infectious stresses such as heat, UV irradiation, and oxidative stress. These stresses have been shown to activate IKKɛ (which is one of the last components in the cascade) and cause it to activate NF-κB (Nuclear factor-kappa B). When activated, this protein moves into the nucleus where it works with other transcription factors to promote the expression of genes that trigger inflammation. It is important to note that these events happen within minutes of your body detecting CDR triggers. 


Inflammation is a vital part of the CDR cascade. It’s what helps cells fight off disease, but there are consequences if it goes on for too long or isn’t properly regulated.  Left unchecked, inflammation can lead to several chronic conditions. 

 Inflammation has been linked to cardiovascular disease, arthritis, atherosclerosis, type 2 diabetes, Alzheimer’s disease, and even depression. One of the most well-known links between inflammation and chronic illness comes from the research of Dr. Robert Ader. In 1974 he conducted a study in which two groups were given an antitoxin to protect against poison. 

 Group A only received the treatment, while group B also had their spleens removed beforehand to prevent their immune systems from mounting an inflammatory response. After receiving the antitoxin both groups were then injected with the poison. However, unbeknownst to them this second injection was not actually poisonous but just saline solution therefore they should not have gotten sick. 

To the surprise of the researchers, group B got just as sick as group A even though they did not have an immune system. Basically, because their bodies had already mounted an inflammatory response when injected with the saline solution it was interpreted by their brains to be a poison so they could become ill. This example is just one of many that illustrate how chronic inflammation can lead to the development of disease.


The answer to this question is multifactorial. First, it’s important to avoid or control infections with your immune system because that is what triggers the response in the first place.  

Second, it’s also best to take care of your body. This means eating a healthy diet, exercising regularly, practicing stress management, and more. 

Third, optimizing your immune system is important.  The better it functions the less likely you are to succumb to disease and the more effective it will be at fighting off infections.

Fourth, protect your cells from damage and stress by limiting exposure to toxins and sources of oxidative stress such as UV radiation and environmental pollutants. This includes using antioxidants that can directly neutralize free radicals before they do damage: vitamin C, vitamin E, manganese, selenium, copper, zinc, and more.

Finally, genetic variation also determines how many times your immune system can mount a CDR response before producing dysfunctional cells. This means that although the danger responses in everyone are the same there is a big difference in their potential scope because of individual genetics. Different SNPs have also been linked to an impaired danger response.

Although the danger response is an important part of fighting infections, it can also be responsible for chronic inflammation which has been linked to many health problems. Fortunately, there are things you can do to prevent this from happening. By implementing lifestyle changes you can help your body fight off disease while simultaneously protecting your cells from damage. 

How can the Institute for Human Optimization help you? At IfHO, we utilize a personalized, precision-based approach to medicine. Precision Medicine acknowledges individual differences in genes.  By having a better understanding of the individual’s genes and making therapeutic decisions based on their genetics, we can work together to drive CDR in a desirable direction.   

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