The Industrial Revolution brought about significant lifestyle changes, leading to a mismatch between our evolutionary adaptations and modern environments, known as “evolutionary mismatch theory”.
This mismatch contributes to the prevalence of autoimmune diseases such as obesity, diabetes, heart disease, Alzheimer’s, and cancer, as gene variants that once provided survival advantages now predispose us to these conditions (1, 2, 3).
Modern stressors exacerbate these issues by promoting chronic inflammation and metabolic dysfunction. Understanding evolutionary mismatch and mitochondrial health is essential for addressing contemporary health challenges.
Mitochondrial Dysfunction, Inflammation and Impact on the Gut Microbiome
Mitochondria, the powerhouses of the cell, play a pivotal role in maintaining cellular homeostasis through ATP production. Mitochondrial dysfunction, characterized by impaired oxidative phosphorylation (OXPHOS) and reduced ATP output, is a central feature of modern lifestyle-related diseases.
Dysfunctional mitochondria produce excess reactive oxygen species (ROS), leading to oxidative stress, which damage cellular components and trigger inflammatory pathways (4).
In immune cells, mitochondrial dysfunction impairs energy metabolism, leading to altered cytokine production and immune cell activation. This dysfunction skews the immune response towards a pro-inflammatory state, promoting chronic inflammation and autoimmune pathology (5, 6, 7, 8).
In the gut, mitochondrial dysfunction exacerbates dysbiosis by creating an inhospitable environment for beneficial microbiota and promoting the growth of pathogenic species.
Impaired ATP production by mitochondria affects epithelial cells in the gut, weakening the mucosal barrier and allowing translocation of bacteria and toxins.
This "leaky gut" condition further amplifies immune activation and inflammation, creating a vicious cycle that perpetuates microbiota imbalances and autoimmune disorders (8, 9).
Modern lifestyle health disruptors
A wide range of modern lifestyle factors converge to disrupt this delicate balance, leading to mitochondrial dysfunction, which causes alteration of the cellular energy balance and immune responses, fostering a pro-inflammatory environment.
Among these factors, western diets containing highly processed foods and sedentarism are well-known (10,11). Here we cover other factors that affect mitochondrial function and the gut, leading to inflammation, which may be less known:
1) Inadequate Sunlight Exposure and artificial blue light
Modern indoor lifestyles limit sunlight exposure, leading to widespread vitamin D deficiency. It has been reported that 30-50% of both children and adults in the United States, Canada, Europe, Australia, New Zealand, and Asia are vitamin D-deficient (12).
This deficiency is associated with a wide range of diseases including cancer and many autoimmune diseases (reviewed in 13). Vitamin D deficiency has been associated with increased intestinal permeability and susceptibility to infections, promoting microbiota imbalances and inflammation (14), hence leading to disease.
Additionally, exposure to artificial blue light from screens and LED lighting disrupts circadian rhythms and melatonin production. Disrupted melatonin production can lead to mitochondrial dysfunction, characterized by impaired ATP production and increased oxidative stress. This dysfunction exacerbates inflammation and alters gut microbiota composition, promoting dysbiosis and gastrointestinal disorders, leading to disease (15).
Current National Institutes of Health (NIH) guidelines recommend maintaining optimal levels of Vitamin D through a combination of diet, adequate doses of vitamin D supplementation (which will be discussed in future articles – stay tunned!), and solar UVB irradiation (16).
Scientifically backed guidelines for solar UVR exposure recommend at least 15 minutes of daily sun exposure between 10:00 and 15:00 from May to September for adolescents and adults (17). These recommendations can vary based on latitude, skin pigmentation, age and other factors.
The descriptive statistics for average Daily MUSE scores representing Minutes of Unprotected Sun Exposure for separate body sites (from scalp to feet) described a maximum average of 20 minutes of unprotected exposure for the face (18).
Importantly, the UVR needed for vitamin D synthesis is much lower than that required for sunburn, as pre-vitamin D production reaches its peak quickly (19). Exposure time should also be adjusted based on the local UV Index (UVI), which is available online.
2) Electromagnetic Fields (EMF)
EMF exposure from technological devices induces oxidative stress and mitochondrial dysfunction. This stress impairs mitochondrial ATP production, promoting inflammation and disrupting the gut microbiota balance (20).The resulting microbiota imbalances contribute to increased gut permeability and inflammation, leading to autoimmune diseases.
An extensive review covered several studies with appropriate methodologies that reflect the capacity of EMFs to cause adverse health effects, including reproductive health, the nervous systems or cancer. In this review, it was concluded that even though further and more comprehensive studies should be performed, several credible mechanisms like oxidative stress have been demonstrated in many studies as the explanation behind the adverse health effects caused by EMFs (21).
Other than lowering EMF exposure as much as possible, several lifestyle habits can be adopted to reduce oxidative stress, such as regular exercise, ingesting nutrients or taking supplementation high in antioxidants, such as omega-3 fatty acids found in fatty fish oils, vitamin C and E, glutathione, and coenzyme Q10 (22). Omega-3 supplements decrease circulating oxidative stress markers, improving mitochondrial function (free radical source) and reducing inflammation (23), as reported by a very recent study.
3) Endocrine Disruptors
Endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) present in plastic and phthalates interfere with hormonal regulation. These chemicals disrupt the gut microbiome by mimicking or blocking natural hormones, leading to dysbiosis and increased gut permeability.
EDCs, along with pollutants and obesogens, increase fat accumulation, inflammation, and adipocyte dysfunction, contributing to metabolic disorders and autoimmune diseases. Mitochondrial dysfunction plays a crucial role in these processes, as EDCs impair mitochondrial function, exacerbating inflammation and metabolic imbalances (24).
Reducing the use of plastics in contact with food and drinking water, as well as using EDCs-free cosmetics and health products is recommended to reduce the EDCs-related adverse health effects.
4) Stress
Chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in sustained cortisol release. Elevated cortisol disrupts the gut-brain axis, altering gut microbiota composition by reducing beneficial bacteria like Lactobacillus and Bifidobacterium while promoting pathogenic species.
This dysbiosis contributes to gut inflammation and permeability, a precursor to autoimmune disorders. Stress-induced mitochondrial dysfunction impairs ATP production, exacerbating inflammation and microbiota imbalances (25).
A wide range of stress and anxiety-relief lifestyle habits include meditation, breathing exercises to promote activation of the parasympathetic nervous system (26), psychological techniques such as EFT (27), regular exercise, adequate nutrition or supplementation with Ashwagandha, L-theanine present in green tea or passion flower (28).
5) Loneliness and Social Isolation
Loneliness and chronic social isolation are associated with upregulated lipid synthesis and a metabolic switch from OXPHOS to glycolysis. Loneliness leads to chronic HPA axis activation, elevated cortisol, increased blood glucose, and insulin resistance, promoting unhealthy habits and reducing satiety signalling (28).
Supplementation and Mitochondrial Support
Given the impact of modern lifestyle factors on mitochondrial function and health, targeted supplementation has been explored as a potential strategy to mitigate these effects (29).
Nicotinamide riboside (NR), a form of vitamin B3, has gained attention for its ability to enhance NAD+ levels, a critical coenzyme for mitochondrial function. NAD+ plays a pivotal role in cellular energy metabolism and redox reactions, and its depletion is associated with mitochondrial dysfunction and inflammation (30).
Many pre-clinical and clinical studies have demonstrated the health benefits and safety of long-term NR supplementation in humans (32, 33). Interestingly, a recent study showed that NR supplementation reduced markers of inflammation and improved insulin sensitivity, highlighting its potential for mitigating the impact of modern lifestyle factors on health (32).
By boosting NAD+ levels, NR supports mitochondrial function, which can help maintain metabolic health and reduce the risk of chronic inflammation (34). As such, NR supplementation represents a promising avenue for maintaining mitochondrial health and mitigating the adverse health effects associated with contemporary living.
Conclusion
Modern life has introduced numerous factors that disrupt mitochondrial function and overall health. From dietary choices and sedentary lifestyles to exposure to pollutants and artificial light, these elements collectively contribute to mitochondrial dysfunction, inflammation, and chronic disease.
Understanding the role of mitochondria in health and disease underscores the importance of strategies aimed at supporting mitochondrial function, such as implementing healthier lifestyle habits and using supplementation to reduce the evolutionary “mismatch” and support our physiological needs.
Therefore, supplementation with compounds such as NR, alongside lifestyle modifications, can offer significant benefits, promoting resilience and reducing the burden of modern lifestyle-related health issues.