Blog 19 – The elderly face two distinct hurdles to maintain normal levels of blood sugar (glucose).
These obstacles are age-related
a) loss of skeletal muscle mass and
b) an aberrant stress response.
The previous blog discussed age-related loss of skeletal muscle mass and its influence on glucose levels (see Vicious Cycle – Aging and Declining Blood Sugar Control). This blog will discuss how age-related changes in our stress response adversely affect our glucose level.
Background – The Stress Response
To adjust to stresses (real or perceived threats) in our lives, humans adapt by activation of several excellent physiological mechanisms, one of which is the stress response. The stress response is familiar to all. It is basically described as a “fight or flight” response. When threatened, the stress response kicks in. The result is enhanced awareness (brain/sensory activation) and accelerated functions of several organ-systems. This enables one to “run away or stay and fight”. Once the threat has passed, the stress response dissipates and organ-systems settle back to normal.
In biological terms, the stress response sets off a coordinated activation of multiple key systems e.g. cardiovascular, skeletal muscles and nervous systems. Importantly, stress triggers the brain (hypothalamus and pituitary glands) to stimulate production and release of a main stress hormone, cortisol from the adrenal glands. Because these 3 glands work together, they are referenced as the hypothalamic-pituitary-adrenal axis or HPA axis. Stress also activates the sympathetic nervous system to maximize blood flow to the brain, heart and skeletal muscles.
Cortisol, the “stress” hormone, acts in many ways.
Firstly, cortisol assures the requisite supply of energy-bearing nutrients e.g. glucose and fatty acids to the brain. It does this by stimulating the liver to produce glucose and fat depots to release fats. It also seriously reduces the effects of insulin so that blood glucose remains abundantly high for the needs of the brain, an organ not requiring insulin for its uptake of nutrients, including glucose.
Secondly, cortisol partners with the sympathetic nervous system to assure optimal heart, muscles and brain function. Together, these actions ready the individual to handle stress.
Thirdly, there exist several inhibitory mechanisms that limit the duration and extent of the stress response.
This is a good thing since continued presence of cortisol not only adversely affects glucose and insulin levels but also robs calcium from bones and suppresses the immune system. Regrettably, these effects are more prevalent as one ages.
Effect of Age on the Stress Response
Humans cannot live without cortisol. It circulates in a rhythmic fashion at low levels 24/7. The basal concentration of cortisol is highest in the early morning. Thereafter, cortisol slowly declines throughout the day. Its lowest level occurs late in the night. Stress significantly and transiently elevates the concentration of cortisol above basal values to achieve the “flight or fight” response.
Daily output of cortisol increases
Unlike most other hormones e.g. growth hormone, melatonin, estrogen, that decline dramatically with age, the daily output of cortisol increases with age. This was convincingly confirmed in a lifelong (20-90 years of age) longitudinal study. This study measured 24 hour urinary output of cortisol (normalized to kidney function). It included over 1800 male and female volunteers in the Baltimore Longitudinal Study of Aging (Moffat et al., 2020).
Basal rhythm exhibits elevated levels
Secondly, not only is total production of cortisol increased with age, but the basal rhythmic pattern is maintained at a significantly higher level throughout the day in the elderly compared to young adults. By sampling cortisol levels every 15 minutes or so over a 24 hour period, many small studies provide data supporting this conclusion. Thus even at rest, cortisol levels in the elderly are elevated.
Response to stress is more forceful and persistent
Thirdly, the stress response is exaggerated in the elderly. Activation of the stress response in the elderly results in an age-related elevation of cortisol and a prolongation of the response. This is supported by a meta-analysis of 48 small studies in which cortisol levels were assessed following a physiological or psychological stress in young and elderly individuals (Otte et al., 2005). A meta-analysis selects similar publications based on rigorous criteria. It then statistically combines all study results to achieve a composite statistic with a greater level of confidence. According to this meta-analysis, “older participants showed either increased cortisol secretion or reduced cortisol inhibition in response to a physiological or psychological challenge.”
In other words, in the elderly, cortisol levels are higher for longer periods thereby ensuring higher levels of glucose and extended inhibition of insulin. This puts the elderly at a disadvantage, creates an inability to regulate blood glucose and increases the risk for type II diabetes..
Relaxation Techniques in Preliminary Stages
There is a wealth of data confirming the benefits of progressive resistance exercise. It is a proven way to maintain muscle mass with age and hence preserve control of blood sugar. In contrast, the data identifying a successful strategy to reduce an augmented stress response as well as elevated basal cortisol levels are essentially preliminary. Of considerable interest are techniques of a) yoga and b) mindfulness-based stress reduction.
A meta-analysis reviewed 42 small clinical trials in individuals practicing yoga. The trials used appropriate controls and objective measures (e.g. cortisol concentrations, blood pressure, other stress factors). The analytical results concluded that the practice of yoga is “associated with improved regulation” of cortisol (hypothalamus-pituitary-adrenal axis) and the sympathetic nervous system”(Pascoe et al., 2017).
Only a handful of clinical trials included in the Pascoe et al., (2017) meta-analysis included volunteers over the age of 65. Of these, only one measured cortisol levels; the others measured blood pressure changes before and after yoga therapy. With this limited data, all objective measures and subjective measures (perceived stress) were lowered with the practice of yoga in the elderly.
Mindfulness-based stress reduction is a clinically standardized type of meditation. Unfortunately, there is only one controlled study on the effect of mindfulness on objective measures of stress in healthy elderly. A small study assessed a 3-day retreat of intensive mindfulness compared to a 3-day vacation (Gardi et al., 2022). The former produced better stress reduction regarding perceived anxiety, lower cortisol levels and lower levels of inflammatory factors.
Conclusions
As one ages, it becomes more difficult to maintain glucose levels in an optimal range. This is partly due to the age-related exaggeration of the stress response. The stress response serves us well in our youth. However, modifications that occur with age e.g. higher and persistent levels of cortisol, allow glucose to achieve a stronger and longer presence. These changes create the milieu for prediabetes, elevate the risk for type II diabetes and accelerate normal aging through oxidation. Sadly, potential means to minimize the aberrant stress response e.g. yoga and mindfulness lack adequate evaluation. Large controlled clinical trials with the elderly are sorely needed.
Select References
Gardi C. et al., A short mindfulness retreat can improve biological markers of stress and inflammation. Psychoneuroendocrinology. 135: 105579, 2022.
Moffat SD et al., Longitudinal Change in Cortisol Levels Across the Adult Life Span. J Gerontol A Biol Sci Med Sci. 75: 394–400, 2020.
Otte C et al., A meta-analysis of cortisol response to challenge in human aging: importance of gender. Psychoneuroendocrinology 30: 80-91, 2005..
Pascoe MC et al., Yoga, mindfulness-based stress reduction and stress-related physiological measures: A meta-analysis. Psychoneuroendocrinology. 86: 152–168, 2017.