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Stress and Aging

Have you ever gone through a stressful life event and, after coming out “on the other side,” felt like you’d aged ten years? Research indicates that stress and its impacts on a system called the HPA axis profoundly impacts how we age, starting at the cellular level.

The hypothalamic-pituitary-adrenal (HPA) axis is a network of endocrine glands, hormones, and neurons that regulate numerous physiological processes within the body, including stress resilience, immunity, and energy utilization. Because of this, it plays a central role in regulating biological aging. 

What is the HPA Axis?

The HPA axis comprises three main endocrine glands – the hypothalamus, pituitary gland, and adrenal glands. These glands influence the production of a wide range of hormones, including corticotropin-releasing hormone (CRH) from the hypothalamus, cortisol and DHEA from the adrenal glands, and testosterone, estrogen, and progesterone from both the adrenal glands and reproductive organs. In the face of acute stress, the HPA axis orchestrates the release of glucocorticoids, such as cortisol, that allows the body to mobilize energy to fuel “fight or flight” activity. Once the acute stressor has resolved, the HPA axis inhibits glucocorticoid release, downshifting the body into a balanced “rest, digest, and repair” state. Ideally, we want to spend most of our time in this “rest, digest, and repair” state of being. 

Unfortunately, much of the stress we face today is chronic rather than acute. Concerningly, a growing body of research indicates that chronic stress hastens biological aging, or the aging that occurs as our cells and tissues accumulate damage over time. Those who are biologically “older” than their chronological age are at a heightened risk of experiencing age-associated health declines.

What exactly constitutes “chronic stress?” Examples of chronic stressors that can accelerate biological aging include:

  • Perceived stress (1)
  • Circadian rhythm disruption (2)
  • Insufficient sleep (3)
  • Poor blood sugar regulation (4)
  • A disrupted inflammatory balance (5)

Chronic stress induces HPA axis dysfunction, which can, in turn, adversely impact downstream physiological processes involved in longevity, including immune function, blood sugar regulation, cognition, and hormone balance. 

HPA Axis and Biological Aging

When the HPA axis is not functioning optimally, it can accelerate aging through multiple mechanisms, including:

Compromised immune function: Research indicates that glucocorticoids, such as cortisol, interact with nearly all types of immune cells. Chronic stress reduces the sensitivity of critical immune cells to cortisol signaling, causing the body to secrete ever-increasing amounts of cortisol. (6) Sustained high cortisol levels may disrupt the body’s inflammatory balance, favoring pro-inflammatory pathways such as the NF-κB pathway. This phenomenon of heightened inflammatory signaling and compromised immune function is called “inflammaging.” Alterations in the HPA axis and immune function may make us more susceptible in the face of bugs and other foreign invaders. (8)

Impaired blood sugar regulation: A lack of proper control of blood sugar levels, or the amount of glucose circulating in the bloodstream, is implicated in accelerated biological aging. (9) Elevated blood sugar levels influence aging through several mechanisms, including heightened production of free radicals, the production of advanced glycation end products (AGEs), and pro-inflammatory compounds formed when glucose modifies proteins and lipids. Where does the HPA axis come in? As a glucocorticoid (this word is a portmanteau for “glucose-cortisol-steroid”), cortisol influences blood sugar levels.

Accelerated cognitive aging: Few consequences of aging are more frightening than the prospect of losing one’s mental acuity. Fascinating research indicates that elevated cortisol exerts detrimental effects on cognition, possibly by inducing cerebral changes and decreasing the clearance of misfolded proteins that, in excess, contribute to neurological declines. (10)

Altered hormone signaling: When stress is chronic, the body shifts several cellular processes along the HPA axis, including gene expression and enzyme production, that favors the synthesis of cortisol rather than crucial sex and longevity hormones such as estrogen, progesterone, testosterone, and DHEA. High cortisol levels and low levels of sex hormones expedite the aging process, contributing to age-associated health declines such as poor memory, weakness, fatigue, skin changes, and low libido.

Support for the HPA Axis

In the modern-day world, each of us could stand to show our HPA axes a bit of love, particularly if we want to age with health and vitality. Fortunately, we have several nutrients, including B vitamins and minerals, and potent botanicals available to us to support our HPA axis function and facilitate a healthy aging process.

  •   NAD+: Neurons in the hypothalamus, a small brain region that controls neuroendocrine (brain and hormone) functions, play a critical role in regulating how our bodies age. Regulation of NAD+ biosynthesis significantly impacts hypothalamic neurons, exerting top-down effects on the operation of the entire HPA axis. Without sufficient NAD+, hormone production flags and the HPA axis may be unable to keep up. Optimizing the body’s NAD+ levels thus provides powerful support for the entire HPA axis. (11)
  •   B vitamins: Chronic stress depletes B vitamins because many of the metabolic pathways used to synthesize and secrete cortisol and other hormones and neurotransmitters involved in the HPA axis, such as catecholamines, require B vitamins as cofactors. Replenishing levels of B vitamins helps counteract stress-induced declines and may support resilient HPA axis function. (12)
  •   Minerals: The relationship between minerals and the HPA axis is complex. Aldosterone, a hormone made by the adrenal glands that regulate sodium and potassium, is stimulated by stress along with cortisol. Chronic stress may thus impact mineral balance, depleting the body of the minerals it needs to regulate blood pressure and the HPA axis. (13) Replenishment of minerals may thus aid healthy HPA axis function, particularly during times of high stress.
  •   Ashwagandha: Ashwagandha is an ancient plant originating from the Indian subcontinent with a long history of use in Ayurvedic medicine. It is classified as an “adaptogen,” a botanical that increases non-specific resistance to stress. Research indicates that Ashwagandha helps balance cortisol levels, promoting balanced HPA axis function. (14) It also is shown to support robust DHEA and testosterone levels in aging men, soothes stress-induced agitation, and supports restful sleep, a crucial lifestyle factor that promotes hormonal balance. (15, 16)
  •   Rhodiola: The adaptogen Rhodiola comes from the root of the hardy Rhodiola rosea plant, which grows in the harsh, forbidding climates of the Arctic and northern Europe and Asia. Rhodiola was reportedly used by the Vikings and indigenous Arctic peoples to support resilience in times of stress and to aid libido and fertility. (17) Modern-day scientific research indicates that Rhodiola helps regulate the expression of genes involved in HPA axis function (18)
  •   Panax Ginseng: Panax ginseng is a revered botanical in Traditional Chinese Medicine (TCM). It contains ginsenosides, phytochemicals that may mitigate stress-induced gene expression and bolster levels of DHEA, a crucial longevity hormone. (19)
  •   Astragalus: Astragalus is one of the fundamental, time-honored herbs used in traditional Chinese medicine (TCM). It may support a healthy aging process by safeguarding the brain during times of stress and safeguarding telomeres, the protective “caps” of genetic material at the ends of our chromosomes. (20, 21)

It’s critical to note that while nutrients and botanicals can significantly assist the HPA axis, allowing chronic stress to perpetuate will continue to drain the body’s reserves. It is, therefore, essential to get to the root of the chronic stressors in your life, such as high work-related stress or blood sugar dysregulation, and determine what changes you can make to reduce stressful inputs. Your HPA axis will thank you!

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