In the quest to uncover the key to cultivating vitality as we age, the Hypothalamus-Pituitary-Adrenal (HPA) axis is a promising area of study that helps unlock the secrets to healthy aging. The HPA axis acts as the body’s stress response system and can have both direct and indirect effects on inflammation, immune system function, metabolic health, and endocrine function. ‍

Cortisol is a downstream stress hormone that is regulated by the HPA axis and is released by the adrenal glands (18). Cortisol’s impact on aging is still being uncovered, but research shows a positive correlation between dysregulated cortisol secretion and increased inflammation, physical limitations, and a decline in cognitive health in aging populations.  

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Understanding Cortisol and Its Functions

As a stress hormone, cortisol is a key player of the HPA axis. When our brains detect a threat, it activates the HPA axis which ultimately stimulates the release of cortisol and other stress hormones from the adrenal glands. Cortisol initiates a cascade of physiological responses that get the body ready to either fight off danger or flee from it. It does this by increasing blood sugar levels for a quick fuel source, increasing breathing rate, heart rate, and blood pressure to optimize circulation and oxygen delivery to vital organs and muscles, tamping down inflammation that would otherwise deplete energy reserves, slowing down digestion, and dilating the pupils to enhance vision. In the presence of acute danger, these responses can mean the difference between life and death. When these dangers pass, cortisol levels should be reduced back to baseline. However, in cases of chronic stress, these levels can remain elevated for much longer. 

In the absence of active threats, cortisol is released throughout the day according to its own diurnal rhythm that is primarily dictated by the body’s sleep-wake and light-dark cycles. It rises in the morning, helping to stimulate wakefulness after sleep, peaks mid-morning, and then steadily declines throughout the day to its lowest levels at bedtime to allow for sleep (20). The Cortisol Awakening Response (CAR) is part of the morning rise in cortisol levels. A healthy CAR pattern shows a 50-150% increase in cortisol levels within 45 minutes of waking, helping us meet the demands of the day (20). 

The Cortisol-Aging Connection

A functioning HPA axis is critical to health and wellness. If the HPA axis becomes dysregulated, cortisol levels and its diurnal rhythm are often disrupted, causing important health implications that can lead to chronic disease. This can be especially true in older adults (20).

Multiple cross-sectional and longitudinal studies have demonstrated a positive correlation between advancing age and overall cortisol output (11). The correlation becomes strongest after the age of 60. The reason for this is yet unknown but a plausible explanation is that the effect of accumulated stressors throughout life can lead to steady and persistent changes to HPA axis function and interfere with the body’s ability to respond to cortisol (11). Additionally, these stressors can be compounded by social isolation, physical limitations, grief, and emotional dysregulation, which unfortunately are all too common later in life (11). 

Though the mechanism remains unclear, the impact of cortisol dysfunction on human health and aging appears significant. In aging populations, these effects are exacerbated if accompanied by a flattened cortisol diurnal rhythm and a reduced CAR which have been linked to chronic issues such as hypertension, Type 2 diabetes, depression, and cognitive difficulties (18). 

Cortisol's Impact on Physical Health and Aging

When the HPA axis is functioning well, it helps keep us safe and respond appropriately to stressors throughout the day. However, when the HPA axis becomes dysregulated, the stress response is no longer appropriate and can negatively impact health. As mentioned previously, once a threat passes, the HPA axis should respond by decreasing cortisol levels and other stress hormones, putting the brakes on the physiological cascade it initiated to prepare the body for a fight or flight response. In the presence of chronic stress, this de-escalation doesn’t occur and instead, the physiological changes that were meant to keep us safe can start to cause harm (20). 

Prolonged cortisol levels can cause persistent elevations in blood pressure leading to hypertension, increased blood glucose levels leading to insulin resistance and diabetes, and decreased immune system function which can increase the risk of autoimmune diseases such as rheumatoid arthritis (17). Chronically high cortisol levels are associated with increased levels of depression, anxiety, and cardiovascular disease (20). Chronic stress and aging have their own particular consequences, increasing the risk for muscle loss, frailty, osteoporosis, osteoarthritis, arterial plaques, and dementia. One study found that participants over the age of 66 with dysregulated cortisol levels experienced more functional limitations and increased inflammatory burden than those with normal levels. 

Cortisol, Stress, and Mental Aging

Another important relationship to note is between cortisol and mental aging. Studies have shown that high cortisol levels in cognitively healthy older adults predict future declines in verbal recall. One study was able to demonstrate that participants with the greatest increases in cortisol over time had the lowest verbal recall scores by the end of a 3-year study. 

The link between stress hormones and cognitive health is significant, with Alzheimer’s Disease patients showing increased cortisol levels compared to non-dementia patients. Furthermore, higher levels of cortisol are linked to a more rapid progression of dementia symptoms (24). It is hypothesized that chronic exposure to cortisol from chronic stress can cause hippocampal atrophy and by extension impair memory. Additionally, high levels of cortisol in the brain correspond to increased deposits of the amyloid-beta proteins seen in Alzheimer’s Disease patients as well as increased inflammatory markers which suggests heightened neuroinflammation. 

How to Test Cortisol Levels

Specialty testing can be a powerful tool to help prevent the unwanted health consequences of chronic stress on aging. The main ways that cortisol levels are assessed are through serum, saliva, or urine. 

Serum testing provides a snapshot of the amount of bound cortisol in circulation. It is able to pick up extreme imbalances in cortisol levels that could indicate adrenal disease. It is less ideal for assessing diurnal patterns as it would require multiple draws throughout the day. Additionally, the stress of getting a blood draw can often falsely inflate cortisol levels. 

ZRT and Doctor’s Data offer salivary testing of diurnal cortisol that can be done easily and quickly in the comfort of one’s home. Salivary testing captures the amount of free cortisol in the moment, making it ideal for testing CAR levels which is an essential measure of HPA axis function. 

Urinary cortisol testing also offers the ease of at-home testing. Unlike serum and saliva, it assesses aggregate cortisol levels over a period of time. The advantage of urinary tests, such as the Adrenal Corticoids Profile by Doctor's Data, is that they are able to assess cortisol as well as its metabolites, providing more clues to HPA axis function. 

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Strategies to Manage Cortisol Levels

There are many ways to help reduce cortisol levels naturally. Mindfulness is a common practice employed to help mitigate stress. It is a cognitive skill that centers awareness in the present and promotes acceptance of sensations, thoughts, and emotions. With regular practice, mindfulness can help train our minds to become less reactive and less triggered, easing the burden on the HPA axis and allowing for elevated cortisol levels to decline to baseline (15). There are many ways to engage in mindfulness: from apps for paced breathing exercises and guided meditations to quiet walks in nature and gentle yoga. With consistent practice, mindfulness can help reduce elevated cortisol levels, decrease symptoms of depression and anxiety, increase energy, and improve sleep (15). 

Lifestyle changes for cortisol management are also important. Focusing on nutrient-dense foods with a balance of healthy proteins, fats, and carbohydrates and a low intake of sweets can improve health outcomes and decrease rates of depression (1). The Mediterranean Diet incorporates all of these factors and provides a rich variety of healthy fibers, antioxidants, and omega-3s, all of which can be beneficial for reducing the deleterious impacts of chronic stress (1).

A good night’s sleep is also vital to HPA function. Inconsistent sleep times and too little sleep can over time lead to increased activation of the HPA axis and elevated cortisol levels. A bedtime routine with consistent bedtimes and wake times can help reinforce a healthy diurnal rhythm for cortisol (14). 

Functional Medicine Approach to Cortisol and Aging

The functional medicine approach to cortisol and aging involves a deep investigative dive into the root cause of the issue. This may include an in-depth review of a patient’s history, physical exam, and comprehensive lab testing to find where imbalances are occurring and what can be done to revitalize the stress response system. To get the full picture of HPA axis function, providers may look at the diurnal rhythm of cortisol and CAR in addition to 24-hour levels. Other adrenal hormones such as DHEA and epinephrine may be measured to assess adrenal function. If nutrient deficiencies are a concern, micronutrient panels such as Metobolomix+ offered by Genova Diagnostics, may be run to identify areas of improvement. A complicated problem requires a comprehensive plan. Because of this, there is no one-size-fits-all holistic approach to stress hormone dysfunction. What works well for one patient might not be appropriate for another.

Functional medicine practitioners work with patients to identify the key components of their lives that are affected by chronic stress and work together to find customized solutions that meet the needs of the individual. These solutions often include a focus on nutrition, lifestyle, mental health support, mindfulness activities, and herbs and nutraceuticals to help mitigate stress and strengthen the function of the HPA axis. 

The Role of Supplements and Natural Remedies

Herbal adaptogens can be an effective weapon against the ill effects of chronic stress. Adaptogens are herbs and fungi that improve HPA axis function and the body’s resiliency to harmful stress effects. Indeed, the initial research on adaptogens was done to help identify substances that could help improve the energy and endurance of USSR soldiers under the stress of active war. Some of the most extensively studied adaptogens are eleuthero, rhodiola, and schisandra. All three have been found to be neuro-protective, improve cognitive function under stress, and combat fatigue. They also demonstrate the ability to modulate cortisol levels to optimize HPA function (19). Ashwagandha, also an adaptogen, has been shown to reduce elevated cortisol levels if taken for a prolonged period. 

B vitamins are essential to a healthy nervous system. The B vitamins B6, B9, and B12 are especially important to improving mood and stress response. Appropriate supplementation with a B complex has been shown to increase CAR and improve the diurnal rhythm of cortisol (3).  

Phosphatidylserine is a phospholipid (fatty substance) that makes up part of the cell membrane. When supplemented, phosphatidylserine can lower elevated cortisol levels. It can be an especially useful tool to help blunt unnecessary elevations of cortisol at bedtime in those with sleep disturbances (2). 

Omega 3 polyunsaturated fatty acids can help lower inflammation that is induced by the stress response system. Omega 3s are found naturally in high amounts in fish oil, especially from salmon, herring, and sardines (1). When taken as a food or supplement, omega 3’s can help improve cognition, decrease depressive symptoms, and help protect the neurons in the brain from injury (1).  

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The Cortisol-Aging Connection: Key Takeaways

Chronic stress can have a negative impact on health, especially as we age. Elevated cortisol levels, irregular cortisol diurnal rhythms, and blunted CAR all have been associated with a decline in health, function, and cognition in aging populations. It is essential that we take a comprehensive approach to cortisol management and aging to help prevent these deleterious effects and promote longevity with vitality. Specialty testing offers a way to identify cortisol and HPA dysfunction to better target the root causes of age-related diseases so that we can find solutions that are effective and sustainable.