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Take the driver’s seat with your immune health.

Biotein’s focus on aging and pro-inflammatory cytokines.

Anupra Chandran
Biotein
Published in
7 min readFeb 16, 2021

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The way we approach health is flawed.

We take supplements. We exercise. We try to switch out that Big Mac for a salad. Yet we can barely tell how this is affecting us on the biological level, beyond how we look and feel.

So we assume we’re healthy, until something goes wrong. A symptom of a disease shows up. But that symptom could be the product of decades of biological damage, building up overtime. Just take Alzheimer’s disease, which can start forming 10–15 years before symptoms show.

It’s like if we were driving a bus, using the gas pedal, breaks and steering wheel as best we could, but we couldn’t see the road. We’d only know we were bad drivers once we hit something.

At Biotein, our goal is to open up that window into your health, by providing insights into your aging process using a saliva diagnostic. The accumulation of cellular damage with age is one of the biggest reasons for health problems, like Alzheimer’s, coronary artery disease, and more.

We focus on indicators of biological aging at the level of proteins. These are the molecular versions of gas pedals and breaks, which control the processes of the body.

One of the indicators of age-related damage we focus on at the proteomic level are cytokines. We’re working on an assay to detect levels of pro-inflammatory cytokine regulators, and give better insight into your immune health.

Pro-inflammatory cytokines, the sirens of the immune system 🚨

The immune system is like a network of ambulances, rushing to sites of infection to eliminate it. Cytokines signal to the immune cells that their service is needed, like a blaring siren.

Normally, we think of these signals as helpful. We wouldn’t be alive without them, that’s for sure. But on the flip side, pro-inflammatory cytokines are markers of chronic inflammation. That means that the immune system is constantly creating molecules to fight pathogens, but is unable to regulate itself properly. It’s like if the siren on an ambulance broke, and couldn’t turn off.

That’s why as we age, we have higher levels of pro-inflammatory cytokines like TNF-a, IL-6 and IL-1b in our tissue.

Let’s zoom in.

At a simple level, your immune system involves antigens, B cells, and T cells.

Antigens are molecules displayed on the surfaces of pathogens, like a 911 call for the immune system to pick up.

When this happens, the B cells create antibodies, which latch onto these antigens. This is like a medical record, because antibodies stay in the body after the pathogen is gone. That way, the immune system can remember old pathogens if infection strikes again, and know how to eradicate them. That’s why those who have had diseases like COVID-19 before may be immune to them afterward.

Source: Arizona State University

Although antibodies can create this memory, it’s the T cells that eliminate the pathogen. They’re the paramedics of the body. A specific type of T cell called the Helper-T secretes pro-inflammatory cytokines, creating a signal for cytotoxic T cells to kill infected cells + pathogens. There are also regulatory T cells, which suppress the immune response once the job is done, by producing molecules like anti-inflammatory cytokines.

A T-cell releasing cytokines.

As aging happens, your body has been exposed to many pathogens, and therefore a lot of antigenic stimulation. It’s almost as if the ambulance “loses gas” after all this work, and the immune system starts to become dysregulated.

One of the main shifts that happens is that the number of regulatory T cells, which help suppress immune response, decreases. At the same time, the number of specific Helper-T cells called Th2 cells increases, and (you guessed it) so does the level of pro-inflammatory cytokines.

This creates chronic inflammation. This state of constant high-alert, that can damage the heart, brain, and more.

Just take heart disease, the top cause of death worldwide. Plaques made of cholesterol build up in the blood vessels, which can lead to heart attacks. Chronic inflammation and the secretion of pro-inflammatory cytokines with age can make this worse in the long term. It irritates blood vessels and loosens plaques, leading to blood clots (according to Hopkins Medicine). Decreasing levels of these cytokines has decreased the risk of heart attacks in studies.

What happens during heart disease, especially when chronic inflammation is involved. Source: Gfycat.

Not to mention Alzheimer’s, the most common age-related brain disease. One of the major markers of this disease is a misfolded protein called an amyloid plaque, that clumps between neurons in the brain and disrupts function. Normally, the body is able to clear these plaques through the immune cells of the brain, microglia and astrocytes. During Alzheimer’s, an increased level of pro-inflammatory cytokines dysregulates the ability for these cells to clear the plaques, and stimulates the creation of these plaques instead.

A representation of amyloid plaques in the brain. Abeta = amyloid protein. Crenezumab = an antibody against these plaques. Source: Nature.com.

As we can see, a heightened level of pro-inflammatory cytokines is bad news.

The good news is, we can control some parts of this aging process.

Our lifestyles could have a major impact on chronic inflammation and cytokines. All the more motivation to cut down on the fast food, and replace it with:

Food 🥗

  • Green tea: Molecules called catechins in green tea can suppress IL-1b and the NF-kB pathway. Not to mention it comes in a bunch of fun flavors.
  • Blueberries, apples, cherries, strawberries, oranges, tomatoes, and green leafy vegetables are high in polyphenols, or naturally anti-inflammatory compounds.
  • Nuts have also been proven to reduce inflammation markers, and the risk of cardiovascular disease.

Supplements 💊

  • Fish oil: An Omega 3 EFA, this supplement is recommended by the American Heart Association. Its active ingredients EPA and DHA enhance the production of prostaglandin E3 in the body, a natural anti-inflammatory agent that limits production of cytokines TNF-a and IL-1b.
  • Turmeric: This pigment can suppress the NF-kB pathway, which is involved with regulating production of inflammatory cytokines.
  • Pycnogenol: Also known as maritime pine bark. This substance helps inhibit pathways induced by cytokine TNF-a.
  • Resveratrol: A well-known supplement in the world of aging research, this molecule can inhibit pathways activated by TNF-a and IL-1b cytokines, and can even prevent DNA damage.

Note: if you’re interested in trying out any supplement, it’s best to ask your doctor whether this may interfere with any other medications. Or cause any other safety issues.

Exercise 🏋️‍♂️

  • Aerobic exercise, like running on a treadmill, biking or swimming, seems to be one of the most effective options to reduce chronic inflammation.
  • Multiple studies have been done into the effect of this exercise on older coronary artery disease patients. For example, participants went through 12 weeks of aerobic exercise, and saw reductions in IL-6, IFN-gamma, and IL-1 cytokines, regardless of other factors like body weight.
  • Regular exercise every day can lower basal levels of these cytokines, and ironically, reduce the inflammation associated with acute exercise (or 1 round of this activity).

Still, everyone’s immune system is different. it’s difficult to know how exactly your lifestyle is affecting you, without data.

We’re committed to providing this data through our upcoming saliva diagnostic, and generating personalized lifestyle recommendations.

One day, with the help of insights like these, we can have a world where age-related diseases are prevented before the symptoms start to show. That way, you can not just see the “road” of your health, but become a better driver.

If you’re interested in learning more about the details of our diagnostic + recommendations, stay tuned! We’re currently testing our product and biomarkers in a research setting, and will be revealing more info soon. Sign up for our newsletter on our site to learn more, and in the meantime, check out the sources below.

Stay healthy,

-Anupra Chandran, Chief Research Officer at bioteinresearch.ca👩‍🔬

Sources

Beavers, K.M., Brinkley, T.E., & Nicklas, B.J. (2010). Effect of exercise training on chronic inflammation. Clinica chimica acta; international journal of clinical chemistry, 411(11–12), 785–93.

Blasko, I., Stampfer-Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P., & Grubeck-Loebenstein, B. (2004). How chronic inflammation can affect the brain and support the development of Alzheimer’s disease in old age: the role of microglia and astrocytes. Aging Cell, 3(4), 169–176. https://doi.org/10.1111/j.1474-9728.2004.00101.x

Christodoulidis, G., Vittorio, T.J., Fudim, M., Lerakis, S., & Kosmas, C.E. (2014). Inflammation in coronary artery disease. Cardiology in review, 22(6), 279–88.

Chung, H.Y., Kim, D.H., Lee, E.K., Chung, K.W., Chung, S., Lee, B., … & Yu, B.P. (2019). Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept. Aging and disease, 10(2), 367–82.

Fight Inflammation to Help Prevent Heart Disease. (n.d.). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/fight-inflammation-to-help-prevent-heart-disease

Harvard Health Publishing. (2020, August 29). Foods that fight inflammation. Harvard Health. https://www.health.harvard.edu/staying-healthy/foods-that-fight-inflammation

Maroon, J.C., Bost, J.W., & Maroon, A. (2010). Natural anti-inflammatory agents for pain relief. Surgical neurology international, 1, 80.

Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013). Proinflammatory Cytokines, Aging, and Age-Related Diseases. Journal of the American Medical Directors Association, 14(12), 877–882. https://doi.org/10.1016/j.jamda.2013.05.009

Rea, I.M., Gibson, D.S., McGilligan, V., McNerlan, S.E., Alexander, H.D., & Ross, O.A. (2018). Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Frontiers in immunology, 9, 586.

Younes, L., Albert, M., Moghekar, A., Soldan, A., Pettigrew, C., & Miller, M. I. (2019). Identifying Changepoints in Biomarkers During the Preclinical Phase of Alzheimer’s Disease. Frontiers in Aging Neuroscience, 11, N/A. https://doi.org/10.3389/fnagi.2019.00074

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