Does cortisol production increase with age? What the science says

Studies have consistently shown that mean cortisol levels increase by 20–50% between the ages of 20 and 80. This elevation is linked to changes in the hypothalamic-pituitary-adrenal (HPA) axis, impacting how the body manages stress. Understanding whether and why cortisol production increases with age is crucial for managing age-related health challenges.

Quick Summary

Mean cortisol levels increase with age, accompanied by a flattening of the hormone's daily rhythm. This is driven by altered function of the HPA axis and decreased negative feedback. The resulting hypercortisolemia is linked to various health concerns, including cognitive decline, metabolic changes, and impaired immunity.

Key Points

• Mean Cortisol Levels Increase with Age: Studies show an increase in average cortisol concentration as people age, with some research indicating a 20-50% rise between ages 20 and 80.

• Diurnal Rhythm Flattens: The daily cycle of cortisol release becomes less pronounced with age, resulting in higher levels at night and a blunted peak in the morning.

• HPA Axis Feedback Loop Impairs: The body's stress-regulating system, the HPA axis, becomes less sensitive to negative feedback, causing it to remain active for longer periods.

• Elevated Cortisol Links to Health Issues: Chronically high cortisol is associated with increased visceral fat, insulin resistance, bone loss, and cognitive decline.

• Compounding Effect of Stress and Aging: Chronic stress and age can have a synergistic effect, worsening the impact of hypercortisolemia on metabolic and cognitive health.

• Other Hormones Decline with Age: In contrast to cortisol, hormones like DHEA and aldosterone decrease significantly with age, leading to an increased cortisol/DHEA ratio.

The HPA Axis: The Body's Stress Response System

The Hypothalamic-Pituitary-Adrenal (HPA) axis is the body's central stress response system. It is a complex network of signaling pathways that regulate the production and release of cortisol. When the body perceives a stressor, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to produce adrenocorticotropic hormone (ACTH). ACTH then travels to the adrenal glands, prompting them to secrete cortisol. Cortisol helps the body manage stress by providing energy and regulating inflammation. Normally, once the threat passes, cortisol levels rise and trigger a negative feedback loop that shuts down the HPA axis, restoring balance. With aging, this delicate system begins to show wear and tear, and this feedback loop becomes less efficient.

Age-Related Changes in Cortisol Production

Research has demonstrated that the aging process profoundly affects the HPA axis, leading to notable changes in cortisol production and regulation. The overall effect is a higher mean level of cortisol exposure over time, a phenomenon that has significant downstream consequences for health.

• Higher Mean Cortisol Concentrations: Several studies confirm that mean 24-hour cortisol levels are higher in older adults. For instance, research on individuals aged 20-80 found a 20-50% increase in mean cortisol levels across that age range. This is likely due to the HPA axis becoming less sensitive to negative feedback, meaning it doesn't shut down cortisol production as effectively as it once did.
• Blunted Diurnal Rhythm: The typical pattern of cortisol secretion involves high levels in the morning (the cortisol awakening response) followed by a gradual decline throughout the day and lowest levels at night. With age, this rhythm becomes flatter, with an attenuated morning peak and a higher evening nadir. This blunted rhythm is associated with frailty, cognitive decline, and metabolic issues.
• Impaired Negative Feedback: The feedback mechanism designed to regulate cortisol becomes impaired with age. The hippocampus, which helps inhibit the HPA axis, is particularly vulnerable to the effects of chronic stress and elevated cortisol. Over time, this can lead to hippocampal atrophy and an inability to properly turn off the stress response.

The Role of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)

Another contributing factor is the increased activity of the enzyme 11β-HSD1 in various tissues throughout the body, including the central nervous system, bone, and skin. This enzyme converts inactive cortisone into active cortisol, leading to elevated local cortisol availability. This localized increase is thought to contribute to several age-related conditions, including cognitive decline, osteoporosis, and muscle wasting.

Comparing Adrenal Hormone Changes with Age

Feature	Cortisol	DHEA & DHEAS	Aldosterone
Effect of Aging	Mean levels increase. Diurnal rhythm flattens, with a higher evening nadir.	Profound decrease over time. Levels can drop by as much as 70-80% by age 70-80.	Basal levels decrease, particularly in response to stimulation.
HPA Axis Regulation	Negative feedback becomes impaired, leading to prolonged activation.	Decreased secretion in response to ACTH stimulation.	Reduced activity of the renin-angiotensin-aldosterone system (RAAS).
Systemic Consequences	Visceral obesity, insulin resistance, bone loss, cognitive decline, impaired immunity.	Potential decline in immune function, muscle strength, and bone density.	Drop in blood pressure with positional changes (orthostatic hypotension).

Consequences of Elevated Cortisol in Older Adults

The chronically elevated cortisol levels observed with aging have multiple adverse effects on the body's systems, contributing to many of the common health problems associated with getting older.

Metabolic and Body Composition Changes

• Visceral Obesity: Higher cortisol levels promote the accumulation of visceral fat (abdominal fat), increasing the risk of cardiovascular disease and metabolic syndrome.
• Insulin Resistance: Cortisol is a catabolic hormone that affects glucose metabolism. High levels are associated with insulin resistance and an increased risk of developing type 2 diabetes in older adults.
• Muscle Loss: Elevated cortisol contributes to sarcopenia, the age-related loss of muscle mass and strength. This is partly due to its catabolic effects, which break down muscle tissue.

Cognitive and Neurological Effects

• Hippocampal Damage: The hippocampus is sensitive to chronic cortisol exposure. The persistent overproduction of cortisol can cause neuronal damage and atrophy in this area of the brain, affecting memory and cognitive function.
• Increased Risk of Dementia: Elevated salivary and urinary cortisol concentrations are correlated with poorer cognitive function and an increased risk for neurodegenerative diseases like Alzheimer's.

Skeletal Health

• Osteoporosis: High cortisol levels inhibit bone formation and stimulate bone reabsorption, accelerating the decline in bone mineral density. This increases the risk of osteopenia and osteoporosis.

Immune System

• Impaired Immunity: Chronic hypercortisolemia can suppress the immune system, leading to altered immune function. It is associated with a weakened response to inflammation and an increased risk of infection.

Conclusion

In conclusion, mean cortisol production does tend to increase with age, driven by changes in the HPA axis and a less sensitive negative feedback loop. This leads to a flattened diurnal cortisol rhythm and heightened overall exposure to the hormone. This age-related hypercortisolemia contributes to various health issues, including metabolic disturbances, cognitive decline, and reduced immune function. However, factors like stress management and exercise can help moderate these hormonal changes. The intricate relationship between the aging HPA axis and its health impacts underscores the need for continued research into healthy aging. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00054/full

Frequently Asked Questions

What is the HPA axis and how does it relate to aging?

The HPA (Hypothalamic-Pituitary-Adrenal) axis is the body's central stress response system. With aging, this system becomes less sensitive to negative feedback, leading to prolonged activation and higher average cortisol levels.

How does the daily cortisol rhythm change in older adults?

In older adults, the normal daily cortisol rhythm, with high morning and low evening levels, becomes flatter or blunted. This means the morning peak is less pronounced and the evening levels are higher than in younger adults.

What health problems are linked to higher cortisol levels in old age?

Higher cortisol levels in older adults are linked to a variety of health issues, including increased visceral obesity, sarcopenia (muscle loss), insulin resistance, osteoporosis, and cognitive impairment.

Does everyone experience the same cortisol changes with age?

No, there is significant individual variation in how cortisol changes with age. Factors like genetics, chronic stress exposure, and lifestyle choices can all influence an individual's trajectory.

Are there other adrenal hormones that change with age?

Yes. While cortisol tends to increase, other adrenal hormones, such as dehydroepiandrosterone (DHEA) and aldosterone, significantly decrease with age. This creates a high cortisol-to-DHEA ratio, which has negative health implications.

Can exercise help manage cortisol levels as we age?

Yes, exercise can be a beneficial tool for managing cortisol levels in older adults. Studies indicate that regular physical activity can help lower high cortisol levels.

What are some practical ways to mitigate the effects of high cortisol?

Strategies include stress management techniques (like mindfulness or meditation), regular exercise, maintaining a healthy sleep schedule, and focusing on social connections to improve overall well-being.