Much like us, cells also experience stress from various sources and the outcome can translate into serious diseases, we call this cellular stress.
Key Points
- Cellular stress can be caused by several factors, including chemicals, UV light, lack of oxygen or nutrients and extreme temperatures.
- Cellular stress can lead to diseases like diabetes, atherosclerosis, heart disease, cancer, and inflammatory conditions
- Aging has also been associated with cellular stress, particularly with oxidative stress.
- Oxidative stress results from an imbalance between the numbers of free radicals and antioxidants.
- Free radicals are molecules that are missing an electron and are highly reactive, removing electrons from DNA, proteins and other components of the cell, damaging their functionality.
- Antioxidants are used by the body to neutralise free radicals.
- Oxidative damage occurs after recurrent oxidative stress, when cells are unable to balance their levels of antioxidants and free radicals, leading to cellular damage mediated by excessive free radicals.
Cells need an optimal environment to function, with an ideal temperature, pH and level of minerals and nutrients. Changes to these factors translate into cellular stress, which, in turn, can lead to the development of multiple diseases, including metabolic syndrome, a complex condition associated with increased chances of developing heart disease, kidney failure, stroke, and overall mortality.
What causes cellular stress?
There are many factors that cause cellular stress, either by affecting the accessibility of components needed by the cell, or by directly damaging a cellular component. Some of the most important factors causing cellular stress include:
- DNA-damaging agents – These include some chemicals, UV light and ionizing radiation (e.g. X-rays). These agents trigger genetic repair pathways in cells, depending on how the DNA is affected1.
- Chemical toxins and extreme heat – These two factors can cause protein denaturation when proteins lose their structural integrity and, literally, “fall apart” and do not function anymore. The body’s response to this type of stress involves the so-called unfolded protein response (UPR), and it involves the mitochondria2-3, the most important source of energy of cells.
- Lack of oxygen – Also known as hypoxia, can be caused by some poisons, or by xenobiotics, chemicals like drugs, food additives, and environmental pollutants. These substances directly affect the function of the mitochondria4.
- Lack of nutrients – Starved cells activate a mechanism called autophagy, where the cell literally eats itself. This is a strategy used by the body to survive in extreme circumstances5-6.
- Infections – Any infectious agent can cause stress responses that can potentially affect cells in the body7.
- Oxidative stress – This occurs when there is an imbalance between the levels of free radicals and antioxidants. Oxidative stress can potentially damage fat tissue, DNA, and proteins in our body, potentially leading to a wide range of serious conditions8-9.
All these drivers of cellular stress affect the optimal functioning of our body and can lead to the development of multiple diseases, from metabolic-related conditions to cancer, and neurological disorders.
Focus on Oxidative Stress
The many metabolic reactions that take place in our body are essential for the maintenance of optimal health. However, these reactions are not perfect and can leave waste products, such as free radicals. Reactive oxygen species, reactive nitrogen species, hydrogen peroxide are all types of free radicals. Our body regulates the levels of free radicals with antioxidants, which neutralise free radicals.
From a chemical perspective, free radicals are defined as any molecule that has lost an electron yet is capable of independent existence. This missing electron makes free radicals highly reactive, meaning they constantly seek to restore their missing electron by stealing it from other molecules, like DNA, proteins, carbohydrates, and fats, affecting their functioning9. Antioxidants can give free radicals their missing electron, without affecting their own structure and function.
An excess of oxidative stress causes proteins and fats in our body to change their structure and function, through the process of oxidation. At the level of cells, excessive oxidative stress can lead to oxidative damage, when cells sustain damage due to high levels of free radicals.
Therefore, oxidative stress can influence the development of diseases like diabetes, atherosclerosis, inflammatory dysfunctions, high blood pressure and heart disease, some cancers, as well as neurodegenerative conditions like Parkinson and Alzheimer’s disease.
Oxidative stress has also been shown to play an important role in the process of aging, due to the damaging effect it can have in cells. This idea led to the development of the so-called free-radical theory of aging10, more than 20 years ago. Since then, many studies have found evidence in favour and against it. Today, the consensus is that oxidative stress is just one of the many factors that affect aging11.
Preventing cellular stress
The strong evidence that cellular stress can significantly affect our health highlights the importance of finding ways to prevent or minimize cellular stress.
Our first line of defence against cellular stress involves reducing our exposure to certain environmental factors like:
- Chemicals found in pesticides and household cleaning products;
- Cigarette smoke;
- Excessive sun exposure. This is particularly important in Australia, where UV levels can reach dangerous levels;
- Alcohol consumption. Any amount of alcohol we drink produces free radicals12.
Another important way to reduce levels of cellular stress is to improve our lifestyle. A major factor to be considered is our diet, which can directly affect the production of free radicals and cellular stress. Some important sources of cellular stress include:
Foods rich in fat and sugar
Some of these foods contain certain fats and sugars that, when processed in our body, produce free radicals. Some of the most important foods and cooking practices to consider include:
- Bad fats – Long-chain saturated fatty acids like palmitate and stearate, as well as trans-fatty acids, are known to increase oxidative stress and influence inflammatory processes and the generation of free radicals13-14. Some common sources of these fats include:
- Animal fat – source of palmitate;
- Palm oil, red meat and dairy – source of stearate;
- Milk fat – source of long-chain saturated fatty acids like myristic acid;
- Fast Food, baked goods, and more – are sources of trans-fatty acids15.
- Excessive Sugar – One of the many detrimental effects of excessive sugar consumption (obesity, heart disease, diabetes) involves the development of oxidative
- One research review found that added sugars, such as table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners, all lead to the generation of reactive oxygen species, a type of free radical. The review also found that excessive consumption of foods rich in these added sugars induces the development for multiple heart problems, including atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias16.
- Cooking Oil – look for oils labelled “cold-pressed”, which means it has not been refined. Most vegetable cooking oils are highly processed and refined, which strips them from nutrients and makes them more susceptible to degradation and formation of free radicals (see below). Some great choices for cooking oils include olive and avocado oil, as they have high smoke points and contain healthy amounts of monounsaturated and polyunsaturated fatty acids.
- Re-using cooking oils – This common practice has detrimental effects on your health. A study using rats showed that exposure to cooking oil re-heated three times not only produced free radicals but also caused damage in various organs. Rats treated with this oil had significant damage in their jejunum, colon and liver17.
Rancid vegetable oils
Oils go through the process of rancidification when their molecules get oxidise due to exposure to air, light, moisture or bacteria. Common sources of rancid oils include industrial vegetable oils, like canola, soybean, peanut, and safflower oils, which are high in omega-6 polyunsaturated fatty acids. This type of fatty acid is highly susceptible to damage from light, air and heat18-19.
Natural sources of antioxidants
Western diets are usually poor in natural sources of antioxidants. Increasing the consumption of antioxidant-rich and nutrient-dense foods is the best way to reduce the levels of free radicals in your body20.
Exposure to pesticides
These can be found in different dietary sources. For example, fruits and vegetables are well-known sources of pesticides. In Australia, like in many other countries, produce can have certain levels of pesticides in their skin and flesh. In this Australian government website, you can see different pesticide levels allowed in fresh produce. Some of these pesticides, like organophosphate insecticides, cause oxidative stress through their disruptive effect on the cell’s redox system21.
Exposure to heavy metals
Heavy metals like lead can be found in drinking water, both in public spaces and in your own home. For lead, the WHO has established that there are no safe levels of lead exposure. Testing the water in our home is an important first step to avoid exposure to lead or other heavy metals.
Beyond diet, there are several other factors that you need to consider, which can affect cellular stress. For example, exposure to pathogens, chronic psychological stress, physical inactivity, and alterations to our circadian rhythms can trigger stress responses that lead to oxidative stress. Consulting with your functional medicine practitioner will help you understand what are some important sources of cellular stress in your life.
References
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- Hetz C, Papa FR. The unfolded protein response and cell fate control. Molecular cell. 2018 Jan 18;69(2):169-81. Read it!
- Shpilka T, Haynes CM. The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nature reviews Molecular cell biology. 2018 Feb;19(2):109. Read it!
- Suomalainen A, Battersby BJ. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nature reviews Molecular cell biology. 2018 Feb;19(2):77.
- Galluzzi L, Pietrocola F, Levine B, Kroemer G. Metabolic control of autophagy. Cell. 2014 Dec 4;159(6):1263-76. Read it!
- Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo‐San Pedro JM, Cecconi F, Choi AM, Chu CT, Codogno P, Colombo MI, Cuervo AM. Molecular definitions of autophagy and related processes. The EMBO journal. 2017 Jul 3;36(13):1811-36. Read it!
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- Harman D. Free radical theory of aging. Mutation Research/DNAging. 1992 Sep 1;275(3-6):257-66. Read it!
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