Stress and Ageing

By Emma Coleman / 04 Jul 2019

Dermatology nurse practitioner Emma Coleman explores links between physiological stress pathways and the skin ageing processes

Last year, digital healthcare company Forth conducted a study amongst 2,000 British individuals, which discovered that more than a third feel stressed for one full day every week, and up to nine days each month.1 Additionally, the UK’s Mental Health Foundation found in a UK-wide survey that women are 17% more likely to experience these feelings than men.2 In this article, I will define and discuss the different types of stress and ageing, and provide evidence to support how physiological stress responses can accelerate specific ageing processes.

Understanding stress

The term ‘fight or flight’ originated in 1929 and was used as a universal term to describe historical animal and human responses to threat, based on universal instincts for survival and for which living creatures had adapted over many centuries.3 The sympathetic branch of the autonomic or involuntary nervous system is activated during threatening scenarios, leading to complex chemical responses causing visible stress responses such as sweating, pupil dilation and trembling, as well as internal bodily changes including bronchodilation to increase gaseous exchange, tachycardia, raised cardiac output and heightened blood glucose levels.4

Today, stress has been described by the Mental Health Foundation as, ‘Our body’s response to pressures from a situation or life event.’ If our stress response is activated repeatedly or it persists over time, the effects can result in wear and tear on the body.5 It was also described by psychologist Dr Gillian Butler as, ‘A particular relationship between the person and the environment, appraised by the person as taxing or exceeding his or her resources, endangering his or her wellbeing’.6

According to primary healthcare company Copeman Healthcare, stress can often present itself in many forms including:

  • Physical: headaches, tension
  • Mental: memory issues, anxiety
  • Emotional: agitation, mood swings
  • Behavioural: eating and sleeping disturbances4

Interestingly, the three most commonly reported UK stress triggers are financial concerns, work and health worries.1 Stress varies based on an individual’s perception of what is stressful and their perceived abilities to cope. Human sympathetic nervous system stress responses are designed for short term situations and vary widely depending on individual perception, suggesting that one person may cope better than another when placed under the same stress and whether the stress is acute or chronic. If it exceeds the body’s ability to respond, system damage can result.3,7 A study that compared hair cortisol concentrations (HCC) in both identical and non-identical twins demonstrated that stress perception and responses are hereditary.8 The study shows that in 72% of subjects, HCC was an inherited trait. 

The research also provides evidence of a link between perceived stress, neuroticism and depressive symptoms with genetic factors. Although more large scale, long term studies are required, these findings highlight that stress perception is part of our genetic makeup and will likely vary widely between individuals.8

Skin ageing due to stress

There is much evidence to suggest that both acute and chronic stress directly impacts skin’s ageing processes.9-12 This is caused by hypothalamic-pituitary-adrenal (HPA) axis disruption, leading to neurogenic and inflammatory response triggers at skin level.13 Additionally, skin actively participates in the body’s stress response.14 The main clinical symptoms of skin ageing are wrinkle formation, hyperpigmentation and loss of elasticity.15 Skin and its appendages are highly sensitive to environmental changes and act as stress and anxiety response mediators.14 Causes of ageing can be classified into two categories:

  • Intrinsic: ageing from natural, physiological changes over time, usually genetically pre-determined16
  • Extrinsic: influenced by UVA and UVB, chemical and pollution exposure, repetitive muscle movements, diet, sleep and overall health16,6

The classification of stress is also two-fold:

  • Internal stress: where inner thoughts and feelings crowd the mind, leading to feelings of sadness and anxiety, unrealistic expectations, uncertainties and self-esteem issues17
  • External stress: caused by situations arising around us, often beyond our control such as employment or family changes and trauma17

One controlled murine study demonstrated that a stressed mouse group developed UV-induced neoplasia at a much faster rate compared with the non-stressed control group.18 With this in mind, when assessing patients for stress levels, it is important to explore their exposure to physical stressors including UVA and UVB light and air pollutants including carbon monoxide, cigarette smoke and sulphur oxide, which in combination with stress may further negatively impact skin’s ageing process.19-21

Hyperpigmentation and melasma

Cortisol is the primary human stress hormone, and when its levels are heightened, epidermal and hair follicle keratinocytes, melanocytes, sebocytes, and mast cells respond via the HPA axis by secreting corticotropin-releasing hormone (CRH).22

CRH is pro-inflammatory, acting to prevent keratin cell synthesis whilst promoting mast cell degranulation.23 Under these circumstances, melanocytes and dermal fibroblasts increase production of adrenocorticotropic hormone (ACTH) and corticosterone, creating a chain where interleukin-18 production in keratinocytes, alongside melanocyte cell production, is stimulated.22

Melanocyte production is further accelerated by raised levels of alpha-melanocyte stimulating hormone (a-MSH).14 Although minimal, there is evidence to suggest a link between sudden onset of human melasma and acute emotional stress.24 Adding to this is heightened TYR gene activity, coded to promote further melanocytic proliferation through production of tyrosinase, leading directly to hyperpigmentation.25

Wrinkle formation

Rhytids form where there is reduction in dermal and epidermal thickness.26 The rhytids may be static (visible without expression)27 or dynamic (observed at all ages and appearing with expression).28 There is evidence that suggests links between stress-induced inflammation and mitochondrial defects, directly contributing to wrinkle formation.Mitochondria can be described as the ‘power house’ of cells as they manufacture energy to drive all cellular functions, so it follows that mitochondrial disturbances disrupt protein production, leading to decline in autophagic degradation and an increase in reactive oxygen species (ROS), cellular organelle deterioration and ultimately, mitochondrial DNA (mtDNA) damage.29

One study provided evidence that depleted mtDNA function produced in mice through induction of dominant-negative mutation in the polymerase domain of POLG1, alongside the introduction of doxycycline to further impair mitochondrial function, directly resulted in formation of wrinkles and inflammatory infiltrate at histological level; interestingly, with the removal of doxycycline the murine mtDNA disfunction was reversed over a one-month period.9 

Another study exerted sustained overcrowding onto mice to create a stressful environment, and found that mild wrinkle formation, dryness and impaired barrier function were a result.30 Furthermore, mtDNA disfunction and epidermal stem cell function are thought to be co-dependent, directly causing skin ageing.31 In another trial, elevated epinephrine (also known as adrenaline), norepinephrine and cortisol levels in acutely stressed mice led to increased cellular DNA damage five-fold.12 The stress hormones also disrupted DNA repair and altered the cell cycle, highlighting the importance of cortisol homeostasis in wrinkle prevention.12

Loss of elasticity and dryness 

Human and murine studies have provided evidence that stress impacts skin barrier function, causing it to heal poorly and appear flaky, dry, dull and more noticeably wrinkled.32,33 The exact mechanism is unknown, although lipid production is an essential part of restoring and maintaining stratum corneum health and integrity, and there is evidence to support that stress-induced corticosteroids inhibit lipid synthesis by reducing lamellar body number.34 Elastin and collagen are structural proteins produced in the dermis by fibroblasts, which help to maintain skin firmness.35 Reduction in these fibres results in skin laxity, giving an overall impression of ageing. Raised calcium levels caused by heightened epinephrine disturbs fibroblast function and thereby collagen and elastin synthesis.36

More recently, various studies have highlighted links to telomere shortening with specific causes of psychological stress, including relative caregiving, childhood adversity and domestic violence.14,37 Telomeres act as nucleoprotein ‘caps’, helping to maintain chromosomal integrity, and shortening can lead to the disruption of mitochondrial biogenesis, stem cell activity and ROS production.37

Adapting your in-practice technique

Many patients lead a busy and stressful life and some of my patients often arrive breathless, barely able to speak having just served dinner and put the kids to bed, or having rushed from the station after a twelve-hour working day, for example. Some have even arranged an appointment with me at 6.30am to accommodate family and work commitments. Assessing patients’ behaviours and state-of-mind clues, as well as what they are saying, must be an integral part of the consultation process; patients may appear well on the surface but may be experiencing mental, emotional or behavioural stress symptoms in their every day lives.42 Looking for signs of extreme stress will help to maintain best practice, including patient safety.43

For this reason, when assessing patients I have switched to a holistic consultation process, encompassing the usual relevant medical history but also questions about their lifestyle factors such as diet and sleep patterns, emotional intelligence, and coping mechanisms. This allows me to create an appropriate treatment and advice package as, in my experience, the patient’s mental state can very much determine how they react to a treatment. For example, a highly-stressed patient may be hyper-reactive to a chemical peel due to presence of a compromised skin barrier.32,33

Furthermore, Carter Singh, Hankins et al., explored in their human study in 2006 the psychosocial effects of cosmetic botulinum toxin treatment and observed distress, worry, expectation and dependence in the study group.43 

This study aimed to pave the way for practitioners to better understand the pressures of their patients during and after cosmetic injectables, and create a heightened sense of accountability for these potentially vulnerable patients. As observed in several studies, one extra, perceived pressure on top of an already heightening mountain of stress can have huge consequences for health and wellbeing.6,7 For a patient screened and identified as highly stressed with recognised symptoms,42 I would recommend an initial exploratory and educational chat to identify potential triggers and ways which they can unwind at home first – using lavender essential oil at bedtime for example, or maybe getting their skin conditioned before considering injectables with a course of pampering facials. 

One study found that patients exposed to lavender essential oil during botulinum toxin injections had reduced heart rate post treatment, compared to the control group.44 For this reason, I always burn lavender essential oil in clinic. Another important factor to consider is the effect of chronic stress on the body’s immune responses. According to a study conducted by Maddock and Pariante in 2001, there is evidence to suggest that biofilm formation following dermal filler treatment is more likely to occur in patients with low immunity.45,46 Furthermore, their skin barrier may be impaired, leading to delayed healing times.32,33 For this reason, I do not advocate use of dermal filler to treat a patient exhibiting signs of profound stress and anxiety.

Conclusion

Many of the physiological studies I have drawn upon here are murine-based, highlighting a need for more human studies. Research has demonstrated that physical, combined with emotional stressors, profoundly heighten skin’s inflammatory response, so it is imperative to remind patients to wear daily sunscreen throughout the year. We can’t see stress, but successful treatment outcomes for patients must involve more than treating the evident facial ageing; a comprehensive and holistic initial consultation looking at lifestyle factors with stress and anxiety assessment is a must. 

References

  1. forthwithlife.co.uk, Great Britain and Stress: How Bad Is It and Why is it Happening?, 2018
  2. mentalhealth.org.uk Stressed Nation: 74% of UK Overwhelmed or Unable to Cope At Some Point in the Past Year, 2018
  3. Walter Cannon, ‘Bodily Changes in Pain, Hunger, Fear and Rage: An Account of Recent Research Into the Function of Emotional Excitement,’ 2nd ed, 1929, Appleton-Century-Crofts
  4. Alicia Garside ‘4 Signs of Stress and How to Manage It’ 2019, < https://www.copemanhealthcare.com/resources/4-signs-stress-manage>
  5. mentalhealth.org.uk, Stress: Are We Coping? 2019
  6. Richard Lazarus and others, Stress Appraisal and Coping. Cited by: Gillian Butler, ‘Definitions of Stress’, 1993, Royal College of General Practitioners <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2560943/?page=561>
  7. Hans Selye, The Stress of Life, Cited by: Gillian Butler, ‘Definitions of Stress’, 1993, Royal College of General Practitioners <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2560943/?page=561>
  8. Liz Reitschel and others, Hair Cortisol in Twins: Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes, Scientific Reports 15351, 2017 < https://www.nature.com/articles/s41598-017-11852-3>
  9. Bhupendra Singh et al., Reversing Wrinkled Skin and Hair Loss in Mice by Restoring Mitochondrial Function,’ Cell Death & Disease, 2018
  10. Akihiro Aioi et al., Effect of High Population Density Environment on Skin Barrier Function in Mice, Journal of Dermatological Science, 2001
  11. Massimo Bonora et al., Mitochondrial DNA Keeps You Young, Cell Death & Disease, 2018 <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155168/>
  12. Melanie Flint et al., Induction of DNA Damage, Alteration of DNA Repair and Transcriptional Activation by Stress Hormones. Psychoneuroendocrinology, 2007
  13. Andrea Evers et al., How Stress Gets Under the Skin: Cortisol and Stress Reactivity in Psoriasis Br Journ Dermatol, 2010
  14. Ying Chen et al., Brain-Skin Connection: Stress, Inflammation and Skin Aging, Inflamm Allergy Drug Targets, 2014 <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082169/>
  15. Mina Yaar, ‘Chapter 2: Clinical and Histological Features of Intrinsic versus Extrinsic Skin Aging,’ In: Skin Aging edited by Barbara Gilchrest and Jean Kruttman, 2006
  16. Wilma Bergfeld, ‘The Aging Skin,’ Int. J. Fertil. Womens Med, 1997 <https://www.ncbi.nlm.nih.gov/pubmed/9160214 >
  17. anxiety.org.uk Stress <https://www.anxietyuk.org.uk/anxiety-type/stress/>
  18. Jason Parker et al., Chronic Stress Accelerates Ultraviolet-Induced Cutaneous Carcinogenesis, J Am Acad Dermatol, 2004
  19. Barbara Gilchrest, Photoaging, J Invest Dermatol 2013 < https://www.jidonline.org/article/S0022-202X(15)41893-7/fulltext>
  20. Andrea Vierktter et al., Airborne Particle Exposure and Extrinsic Skin Ageing, Society for Investigative Dermatology, 2010
  21. Miaozhu Li et al., Epidemiological Evidence That Indoor Air Pollution from Cooking with Solid Fuels Accelerates Skin Ageing in Chinese Women, J Dermatol Sci, 2015
  22. Andrzej Slominski et al., Steroidogenesis in the Skin: Implications for Local Immune Functions, J Steroid Biochem Mol Biol, 2013
  23. Theoharis.C. Theoharides et al., Corticotropin-Releasing Hormone Induces Skin Mast Cell Degranulation and Increased Vascular Permeability, A Possible Explanation for its Proinflammatory Effects,’ Endocrinology, 1998
  24. Ronni Wolf et al., Melasma: A Mask of Stress, British Journal of Dermatology, 1991
  25. Gertrude Costin et al., ‘Human Skin Pigmentation: Melanocytes Modulate Skin Color in Response to Stress,’ FASEB <http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.333.8267&rep=rep1&type=pdf>
  26. Gottfried Lemperle et al., A Classification of Facial Wrinkles,Plastic and Reconstructive Surgery, 2001
  27. Moetaz El Domyati, Forehead Wrinkles: A Histological and Immunohistochemical Evaluation,Journal of Cosmetic Dermatology, 2014 <http://mc.minia.edu.eg/research/admin/Publications/21102018Forehead%20Wrinkles%20JCD%202014.pdf>
  28. Tsutomu Fujimura et al., ‘The Preliminary Study of the Relationship Between Facial Movements and Wrinkle Formation,’ Skin Res Technol, 2012 <https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0846.2011.00557.x 18>
  29. Antero Salminem et al., ‘Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process’ Int. J. Mol. Sci. 2013,<https://www.mdpi.com/1422-0067/14/2/3834/htm>
  30. Akihiro Aioi et al., ‘Effect of High Population Density Environment on Skin Barrier Function in Mice.’ J Dermatol Sci. 25, 2001, <https://www.jdsjournal.com/article/S0923-1811(00)00133-X/fulltext>
  31. Massimo Bonora et al., ‘Mitochondrial DNA Keeps You Young,’ Cell Death and Disease, 2018 <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155168/>
  32. Amit Garg et al., Psychological Stress Perturbs Epidermal Permeability Barrier Homeostasis: Implications for the Pathogensis of Stress-Associated Skin Disorders, Arch Dermatol, 2001 (p:53-59)
  33. Peter Elias et al., Barrier Function in K-10 Heterozygote Knockout Mice.J Invest Dermatol, 2000
  34. Ying-Ho Choi and others, Mechanisms by which Psychologic Stress Alters Cutaneous Permeability Barrier Homeostasis and Stratum Corneum Integrity, J Invest Dermatol, 2005 <https://core.ac.uk/download/pdf/82583204.pdf
  35. Amanda Oakley, Terminology in Dermatology, 1997 <www.dermnetnz.org>
  36. Bruna Romana-Souza and others, Stress-Induced Epinephrine Levels Compromise Murine Dermal Fibroblast Activity Through β-Adrenoceptors,’.Exp Dermatol. 2011
  37. Eguin Sahin E et al., Axis of Ageing: Telomeres, p53 and Mitochondria’, Nat Rev Mol Cell Biol, 2012 <http://info-centre.jenage.de/assets/pdfs/library/sahin_et_al-NATURE-03_2010.pdf>
  38. Patricia Oyetkin-White et al., Does Poor Sleep Quality Affect Skin Ageing? Clinical and Experimental Dermatology, 2014
  39. Eung-Ho Choi and others, Mechanisms by Which Psychologic Stress Alters Cutaneous Permeability Barrier Homeostasis and Stratum Corneum Integrity, J Invest Dermatol, 2005
  40. Inja Bogdan et al., Antioxidants Used in Skin Care Formulations, Skin Therapy Letter, 2008
  41. Zoe Draelos, The Science Behind Skin Care: Moisturizers. Cosmet Dermatol, 2018 <https://onlinelibrary.wiley.com/doi/abs/10.1111/jocd.12490>
  42. Alicia Garside ‘4 Signs of Stress and How to Manage It’,2019 <https://www.copemanhealthcare.com/resources/4-signs-stress-manage>
  43. Carter Singh et al., Psychosocial Aspects of Botox in Aesthetic Surgery, Aesthetic Plastic Surgery, 2006
  44. Lisa Grunebaum et al., Effects of Lavender Olfactory Input on Cosmetic Procedures, Journ Cos Dermatol, 2011
  45. Clementine Maddock et al., How Does Stress Affect You? An Overview of Stress, Immunity, Depression and Disease, Epidemology and Psychiatric Sciences, 2001
  46. Wojciech Marusa et al., Probable Biofilm Formation in the Cheek as a Complication of Soft Tissue Filler Resulting from Improper Endodontic Treatment of Tooth 16, Int J Nanomedicine 7, 2012 

Comments

Log-in to post a comment

  • Ms Alma Cantu 28 Jul 2019 / 1:00 PM

    This is a very interesting study and shows just how stress affects both internally and externally issues on skin and well being aspect of the human body! Learning how to help balance out this emotion whether through yoga, breathing exercises and or meditation with essential oils can assist in this factors! Excellent article!