The Two Faces of Oxidative Stress
We’ve all heard that antioxidants support longevity and so does lowering inflammation. Exercise, as we described in our previous article on Exercise and Longevity, also promotes longevity and healthy aging. But what if we told you exercise actually increases oxidation and inflammation? In this article, we discuss the Ox Paradox: Oxidative stress is damaging, yet oxidation is also essential for cellular function. This is exemplified by the case of exercise’s short-term and long-term health impacts.
Energy production versus oxidative damage
When you exercise, your muscle cells need energy to contract and release. To create this energy, oxidative processes happen on a cellular level, producing ATP – the cell’s energy currency – from glucose. These oxidative processes are mediated by a group of molecules that contain oxygen and react very easily with other molecules: reactive oxygen and nitrogen species (ROS). To increase energy production, the amount of ROS also increases. This in turn increases oxidative stress – particularly in high intensity exercise, as demonstrated for example in aerobic exercise (Ebele et al, 2016). The intensity, frequency, and duration of physical activity significantly influence oxidative stress responses (Ferlazzo et al., 2021; Longobucco et al., 2022). It is especially essential to allow for proper post-exercise recovery. Research shows that intense training regimens lacking adequate recovery can lead to cumulative oxidative damage. This may decrease performance over time, increasing the risk of injury (Ebele et al., 2016; Ferlazzo et al., 2021; Pozzi et al., 2010). If the oxidative stress is too high for the body’s natural antioxidant defenses, it can cause damage on a cellular level, accelerating aging and increasing the risk of noncommunicable diseases like cancer (Liguori et al., 2018).
So why is exercise good for longevity, if it increases oxidative stress?
It is anticipated that skeletal muscle is the main source of the production of reactive oxygen and nitrogen species (ROS) during exercise, even though multiple tissues may also play a role (Jackson et al., 2016). Specifically, muscle contractions are thought to trigger the production of ROS in active muscle fibres. This generation of ROS during contraction is linked to negative effects like oxidant damage in various tissues (such as increased lipid peroxidation and protein oxidation) and accelerated muscle fatigue (Di Meo et al., 2019; Davies et al., 1982). However, it is also important for the activation of biochemical signaling pathways that aid in the adaptation of contracting muscle fibres to exercise (Powers et al., 2024). That means production of oxidative stress is an important signal for the adaptation of the body towards training. Oxidative stress is resulting in inflammation triggering multiple signaling pathways involved in the regulation of protein biosynthesis and energy metabolism (Langston & Mathis, 2024). This is demonstrated by the fact that a complete suppression of exercise induced inflammation, for example by taking drugs like aspirin, has been shown to suppress training efficiency (Isenmann et al., 2020).
Moreover, regular moderate aerobic exercise can strengthen the body's antioxidant defenses, creating a scenario where the body adapts to manage oxidative stress more effectively. For example, Siu et al. demonstrated that habitually active individuals show increased resistance to oxidative DNA damage. This indicates that regular exercise training upregulates the expression of antioxidant enzymes (Siu et al., 2011). Chronic training, with sufficient recovery between sessions, can modulate inflammatory markers and improve oxidative stress response over time (Longobucco et al., 2022; Nascimento et al., 2021; Gonzalo‐Calvo et al., 2012). This adaptation underscores a key mechanism in the Ox Paradox: while a single intense workout might induce oxidative harm, consistent exercise can promote resilience against such damage.
Stronger through stress: how mitochondria and antioxidants shape resilience.
Resilience is increased through improved antioxidant mechanisms and mitochondrial function (Mohammadkhani et al., 2023; Davison, 2016). This concept is also known as hormesis: By challenging the body’s capacity to return to internal balance or homeostasis with small stressors, the body’s capacity to manage greater stressors and return to homeostatis increases (Militello et al., 2024). The same concept applies to mitochondrial functioning. Stressing the cellular energy production in mitochondria increases their capacity to return to homeostasis, lowering overall odixative stress and has a long-term positive impact on longevity (Ristow & Zarse, 2010). In some longevity clinics hyperbaric oxygen treatment is applied to the same effect.
With mitochondria playing such an important role in cellular energy mechanisms and oxidative processes, the role of specific "mitochondrial nutrients" has gained attention. Compounds such as astaxanthin, quercitin, resveratrol and curcumin have been shown to ameliorate exercise-induced oxidative stress by enhancing mitochondrial function and reducing the impact of oxidative stress on cellular components (Korivi et al., 2012; Simioni et al., 2018; Polotow et al., 2014). Ensuring you get plenty of antioxidants, for example by incorporating antioxidant-rich foods or supplements into your diet, may enhance recovery after exercise while also protecting against oxidative damage (Ferlazzo et al., 2021; Polotow et al., 2014). This creates a win-win situation, buffering the body from excessive short-term oxidative stress while also allowing the body’s adaptive capacity to oxidative stress to increase via hormesis.
Conclusion: the Ox Paradox and adaptive capacity
In conclusion, the Ox Paradox highlights the body’s adaptive capacity through hormesis, as seen in the complex interplay between exercise-induced oxidative stress and the body's adaptive responses. While intense exercise causes oxidative stress, potentially oxidative damage, regular physical activity fosters resilience and enhances antioxidant defenses, supporting overall metabolic health. The introduction of the term mitohormesis reflects the importance of mitochondrial health and the necessity to balance oxidative processes within the cellular environment. Understanding the Ox Paradox can aid in developing tailored exercise regimens and dietary strategies that maximize health benefits while minimizing the risks associated with oxidative stress.
References
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