In the Goldilocks Zone: Navigating the Balance of Oxidative Stress for Optimal Skin Health

Whether on social media influencers’ pages or in beauty product boxes, warnings of “oxidative stress” are making headlines around the globe. It’s a term that skincare enthusiasts may associate with antiaging skin creams and facial serums, but its significance extends beyond the skin’s surface.

At its core, oxidative stress is the result of an imbalance between free radicals and the body’s defense mechanisms. These free radicals, called Reactive Oxygen Species (ROS), play a role in natural cellular activities but — when in excess — lead to molecular damage. The sweet spot of “not too much, not too little” is a kind of “Goldilocks Zone” where the cells have just enough free radicals to function but not so much that they cause harm.

In other words, it isn’t that our bodies need to be rid of free radicals entirely. On the contrary, our cells need free radicals to communicate, defend against foreign bodies, and perform optimally. If you’re curious about how free radicals function and how you can step into the Goldilocks Zone, this article is for you. In the pursuit of science, skin health, and longevity, we’ll explore how oxidative stress impacts skin aging — and what proactive measures you can take to defy its impact.

What Is Oxidative Stress?

Oxidative stress exists all around us — and, to some extent — within us. Many forms of oxidative stress are harmful to the body, causing the degradation of important macromolecules such as DNA, lipids, enzymes, and carbohydrates. Excessive oxidative stress exacerbates many chronic, detrimental conditions and has links to the pathogenesis of disease and aging.

Picture it as a seesaw — when free radicals, specifically ROS, tip the scale, the consequences can be profound. ROS, with their unpaired electrons, snatch electrons from crucial biological molecules like DNA, setting off a chain reaction of mutations and altered gene expressions.

Some level of ROS is a natural byproduct of cellular activities, originating from the mitochondria — the cellular powerhouses. These tiny structures, responsible for activities like cellular respiration, generate ROS as part of their routine. To maintain equilibrium, our body has developed an intricate network of antioxidant defenses, ensuring that ROS levels stay just right.

Understanding Oxidative Stress and Its Impact on Aging

Prolonged oxidative stress is a phenomenon that plays a major role in skin aging — which is why the term has become ingrained in the skincare industry’s vocabulary. Let’s take a closer look at what the term means, its relationship to skin health, and current cutting-edge interventions.

How Oxidative Stress Happens

Oxidative stress results from an imbalance of free radical molecules in relation to antioxidant defense(s). It arises from the overlap of environmental (extrinsic) and/or internal (intrinsic) triggers and has closely been associated with aging (1). Outside triggers like UV damage or inside triggers like overactive mitochondrial processes are just a few examples of how oxidative stress develops in the body and how it can cumulatively lead to tissue decline and age-related disorders.

Reactive Oxygen Species (ROS) are a type of oxidative stress. Due to their unpaired electron state, ROS are extremely reactive and can negatively affect many critical biological molecules like DNA. When they steal electrons from DNA, it directly leads to mutations, changing how genes are expressed.

Nevertheless, ROS in the body is a bit of a “Goldilocks” situation: it must be just right for homeostasis — in other words, a steady basal state of physiological and biochemical equilibrium. ROS is actually a natural byproduct of the mitochondria, which are the cell’s powerhouses responsible for activities like cellular respiration and normal metabolism. To prevent an excess of harmful free radicals and maintain balance, the body has developed various effective antioxidant defenses.

However, free radical production increases with age (2). The hazardous bonding ability of free radicals destroys macromolecules’ chemical structure and triggers a series of damaged cellular functions. As we age, our intracellular repair system becomes overwhelmed, leading to a gradual decline in both individual cells and the overall organism, eventually becoming uncontrollable.

What Are Cellular Sources of Oxidative Stress?

Reactive oxygen species are molecular factors that influence many physiological changes in the body. ROS can be classified into two primary types: those originating from mitochondria and those from sources outside mitochondria. ROS generated from mitochondria have been linked to the aging process (3), but non-mitochondrial-derived ROS’ impact on aging is still unclear.

  1. Mitochondrial ROS (mtROS): Mitochondrial ROS (mtROS) gradually contribute to oxidative stress, originating from reactions in the electron transport chain during cellular energy production. With age, our mitochondria become less efficient, reducing energy production but increasing mtROS, leading to dysfunction. This inefficiency triggers a vicious cycle of elevated ROS production.
  2. Non-mitochondrial ROS: The degradation of hydrogen peroxide or nitric oxides and their derivatives are situations that produce free radicals, which are promptly neutralized with bystander antioxidants such as ascorbic acid (Vitamin C) or a-tocopherol (Vitamin E) (4, 5).

The Role of Oxidative Stress in Skin Aging

The skin organ is the main barrier against the outside world — the first line of defense against environmental insults. Its primary cell type, keratinocytes (the main cell type of the epidermis), constantly renew to replace any environmentally-damaged cells, maintaining the skin’s integrity.

Oxidative Reactions and Antioxidants

The skin undergoes unstable, oxidative reactions which are countered by systemic antioxidants. This delicate balance ensures the skin’s health, but when disrupted by oxidative stress — overpowering our body’s defenses and disrupting homeostasis — it impacts the regenerative capacity of skin cells. This imbalance sets the stage for premature signs of aging — fine lines, wrinkles, discoloration, uneven texture, epidermal thinning, and loss of elasticity (6).

Decreased Skin Function

Whether due to photoaging or natural aging, decreased skin function can also be directly linked to abnormal (elevated) oxidative stress levels. Oxidative stress destroys the stem cells that maintain the very basic barrier function of the skin, resulting in skin sensitivity, dry skin, development of skin diseases, and elevated risk of skin cancers (7). ROS is arguably one of the most harmful contributors of skin aging.

Hair Follicles and Oxidative Stress

ROS also acts on the hair follicle component of the skin. Premature hair loss and hair graying can be considered symptoms of general skin aging — an often-overlooked symptom of general skin aging. While the underlying mechanisms remain unclear, one leading theory is that oxidative stress targets and destroys the sensitive stem cells for pigment (melanocytes) and disrupts signaling hubs for hair shaft growth (dermal papilla cells) (8,9).

Mitochondrial Dysfunction in Senescent Skin Cells

Mitochondrial dysfunction is a characteristic of senescent skin cells, as reduced oxidative phosphorylation (reduced energy production) has been observed in human fibroblasts that underwent premature senescence conversion and cell cycle arrest in a lab setting (10). Furthermore, the biodynamics of senescent cell mitochondria are also altered, resulting in low ATP synthesis that is otherwise needed for optimal cell function (11). You can read more about mitochondrial health and skin aging here.

Overall, there is sufficient evidence demonstrating that the impaired ability to break down free radical molecules directly results in oxidative stress and skin aging phenotypes.

How Does My Lifestyle Influence Oxidative Stress?

Understanding the sources of oxidative stress is a crucial step toward mitigating its effects. Being familiar with sources of oxidative stress is essential, as many lifestyle choices also influence free radical production. It’s much better to be preventive in nature than to quench free radicals once they have been made over a lengthy stretch of time. Let’s delve into the factors contributing to oxidative stress and explore potential solutions.

Factors Contributing to Oxidative Stress

1. Prolonged Sun Exposure

The Culprit: The sun’s UV rays are a potent source of oxidative stress. Prolonged exposure can lead to the formation of free radicals, triggering damage to skin cells and accelerating the aging process.

Solution: Prioritize sun protection by using broad-spectrum sunscreen with a high SPF (at least SPF 30 or higher), wearing protective clothing, and seeking shade during peak sunlight hours. Regularly check your skin for any growths, changes, or abnormalities, and consult a dermatologist for comprehensive skin health guidance.

2. Tobacco

The Culprit: Smoking introduces a multitude of harmful chemicals into the body, promoting oxidative stress. It not only accelerates skin aging but also heightens the risk of various skin conditions.

Solution: Quitting smoking is the most effective way to reduce oxidative stress caused by tobacco. Seek support from healthcare professionals, join cessation programs, or explore nicotine replacement therapies to increase your chances of success.

3. Alcohol

The Culprit: Excessive alcohol consumption can overwhelm the body’s antioxidant defenses, leading to increased oxidative stress. Overconsumption can contribute to skin aging and a range of skin-related issues.

Solution: Moderation is key. Limit alcohol intake, and ensure you stay hydrated with water to support your body’s detoxification processes. Consider alcohol-free days, and be mindful of your overall consumption.

4. Environmental Pollution

The Culprit: Air pollution exposes the skin to particulate matter and toxic substances, promoting oxidative stress. This can result in a range of skin problems, including premature aging.

Solution: Create a protective barrier by using skincare products that contain antioxidants. Regularly cleanse your skin to remove pollutants, and consider investing in air purifiers for indoor spaces to minimize exposure.

5. Heavy Metals

The Culprit: Exposure to heavy metals like lead, mercury, and cadmium can contribute to oxidative stress, adversely affecting skin health.

Solution: Be conscious of your environment, especially if you work in industries where heavy metals are prevalent. Follow safety protocols, use protective gear, and consider incorporating chelation therapy under professional guidance to eliminate heavy metals from the body.

6. Psychological/Emotional Stress

The Culprit: Chronic stress triggers the release of stress hormones, contributing to oxidative stress and negatively impacting skin health.

Solution: Prioritize stress management through activities such as meditation, mindfulness, yoga, and counseling. Ensure adequate sleep and practice self-care to mitigate the effects of stress on your skin.

7. Certain Medications

The Culprit: Some medications, especially those with photosensitizing effects, can exacerbate oxidative stress and increase susceptibility to skin damage.

Solution: Consult with your healthcare provider about potential side effects of medications. If photosensitivity is a concern, take extra precautions when exposed to sunlight, and consider alternative medications if available.

Dietary Impacts

Oxidative stress at the skin level can also originate from an unhealthy diet; i.e. high protein, carbohydrate and/or [saturated] fat foods are metabolized into free radical molecules inside the body that cause widespread inflammation. Indeed, certain metabolic diseases, such as obesity, display pro-inflammatory signatures in white adipose tissue in addition to low antioxidant defenses and compromised immunity (12, 13).

A longevity diet contains many natural antioxidant food sources that can combat oxidative stress for optimal systemic health that goes beyond skin. This intimate relationship again stresses the importance between diet and health.

What Antioxidants Can I Use for Skin Health?

Beyond dietary and lifestyle interventions, certain antioxidants may be beneficial in mitigating the negative impacts of oxidative stress. These include more advanced, topical antioxidants that  complement sunscreen components, such as Coenzyme Q10 (CoQ10), EUK-8/134/189/207, and Superoxide Dismutase (SOD):

  • CoQ10: This antioxidant plays a key role as a restorative antioxidant and is intricately involved in cellular respiration in aged keratinocytes (14, 15).
  • EUK: All iterations of EUK function as ROS scavengers to reduce oxidative load; the differences between them range from variability in stability and/or half life. EUK-134 is a commercially available SOD/catalase mimetic and functions to reduce free radical exposure. When tested in humans, this molecule supplemented native antioxidant activity for combating oxidative damage in the skin. EUK 189 decreased macromolecule (lipid, nucleic acid) oxidation in aged mice as a result of ROS. EUK-207 is protective against radiation dermatitis, improves wound healing, and detoxifies ROS in a radiation mouse model (23, 24, 25, 26).
  • SOD: Also existing as a commercially available skin product, SOD has been shown to reduce accelerated skin aging by promoting collagen production (16, 17, 18) .
  • Powerhouse foods: Consuming antioxidant-rich foods such as leafy-green vegetables, fruits (abundant in polyphenols), and whole grains have been time-long methods for reducing oxidative stress, inflammation, and infection all over the body and therefore can and will improve skin health in the long run.

Note that topical applications and a healthy diet rich in antioxidants should not be a substitute for sunscreen.