Exosomes, Pheromones, and the Placebo or Nocebo Effect.

Exosomes are little packets of information that cells can send out in one area of the body to cause change in another area or system of the body. Pheromones are chemicals that may be produced by a person, animal or plant, and tend to have a detectable odor.

*Continuation of a series, links in this post: Exosomes & the Placebo Effect.

Olfactory receptors can be very powerful, only tiny amounts of a chemical can activate one. Trauma or pleasant memories can be formed that last a life time, and cause a change when the odor is experienced again. Communication therefore, can be indirect, wordless, but leave a lifelong impact on the brain and body - internally with exosomes carrying microRNA, or externally with released pheromones that others may smell/sense and can also be physically affected by them for life potentially.

Tinier lengths of RNA called microRNA (miRNA) can be carried in the exosome and they can cause messenger RNA, mRNA, to be deactivated, or activated - causing change to occur in the activity that a cell is performing. Messenger RNA is what is being made into proteins by the cell. MicroRNA seems to be a control factor that can prevent mRNA from being transcribed into protein, instead the mRNA is broken down. Immune cells may also be activated by microRNA in a protective way, or cancer cells may send out inflammatory microRNA messages that increase harm by increasing cytokine production. (1)

RNA is normally not supposed to be outside of cells, extracellular, any that is out of place may be inflammatory - a negative for health. Presence of larger quantities of microRNA outside of cells may be able to be used as a lab test to screen for cancer or other disease conditions that have been identified as having excessive microRNA present in extracellular fluid.

"The activation of TLRs with circulating exosomes is consistent with a recent study showing that miRNA21 and miRNA29a secreted by lung cancer cells in exosomes can activate innate immunity via TLR7/8 [22] . In addition, a study by Lehmann et al. [23] showed the activation of TLR7 in macrophages and microglia by extracellular miRNA let-7 leads to cytokine expression and neurodegeneration [23] . It should be noted that we and others have shown that any immunostimulatory RNA sequence, regardless of its origin and structure (e.g. siRNA, miRNA, viral RNA, mRNA), can activate TLR7/8 once it is delivered to the endosomes [5–8] " (1)

The amount of microRNA present in extracellular areas may be a way to screen for cancer, (3), and possibly other disease conditions. (4)

"Accumulating evidence has revealed that microRNAs (miRNA or miR) are extensively involved in cancer progression and suppression by regulating thousands of cancer-associated genes [12]. miRNAs can stably exist not only in cytoplasm, but also in various types of body fluids. Circulating cell-free miRNAs have been shown to have the potential to enable earlier cancer diagnosis and to predict prognosis and response to therapy [13]." (3)

How does this fit in with the placebo or nocebo effect? The idea that you can think yourself well may seem preposterous, but is it? If we visualize our white blood cells becoming more active, might they? Might they become more activated due to other cells sending out exosomes with microRNA messages that promote more protective immune activity?

That is question that each individual has to try for themselves - no one else can think positive for you - though negative messages from an authority figure might be adding a nocebo effect to your thoughts, while a positive message that change is possible might add a placebo effect.

Pheromones are also microRNA; and microRNA can affect our genes, our behavior and our health - and even our growth as a developing fetus too. (8)

"Our results show how pheromone or endocrine signaling pathways can coordinately regulate both developmental progression and cell-fate transitions in C. elegans larvae under stress so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory." (2)

Olfactory receptors, odor receptors, are somewhat unique in how microRNA can control their activity. (6) MicroRNA tends to deactivate genes but can also activate them. MicroRNA is essential in fetal development of the brain and olfactory system, too much can be a negative though. (7)

"MicroRNAs (miRNAs) are broadly important in regulating vertebrate neurodevelopment, and are required in embryonic olfactory differentiation." (7)

Ritual, placebo/nocebo effect and odor chemicals.

Ritual can strengthen the placebo or nocebo effect, and odor may be a factor that has physical effects, not just setting 'a mood' metaphorically, it may help shift a person's mood physically within their body chemistry.

A placebo effect can be strengthened by ritual, which traditionally tended to use aromatic smoke or herbs in addition to chanting or hand motions. Medical rituals of measurements and checking body reflexes may add to a feeling of being helped. Strong chemical odors might add negative toxic effects though. It is worth thinking about air quality, aroma, artwork or images of nature within the decorations, and sound quality in a setting designed for 'health'.

Pheromones are associated with romance and falling in love however they are also part of odor enjoyment, or odor dislike. Trauma like memory associations can develop after a bad stomach upset - this may be protective instinctually against food poisoning risks. Colors and textures, or odors, associated with the feeling of disgust, are also the color of vomit and mucus from a person with a respiratory infection, or the texture of mucus, or the smell of infection. We learned instinctually to avoid certain things. Red is a danger color instinctually, likely because it is the color of blood, and also of fire.

Odors can also have positive associations - the smell of fresh baked cookies may cause a positive feeling to occur. The perfume or aftershave lotion of a loved one may also always bring back a sweet feeling when smelled many decades later..

Remember to stop and smell the roses - or lavender - or Ylang-ylang flowers, (5),

- or whatever you enjoy and makes you feel positive! It may be helping your health in physical ways. The color blue and green tends to make me feel good, and seeing greenery or flowers. We tend to become better at stress coping as we mature - older may be wiser if you pay attention to what makes you feel well overall, and less well. (9) Temporary bursts of dopamine can feel exciting, but is not the same as a general sense of stable energy for physical and mental work.

Clinging to worry or hurt or fear is keeping yourself in the nocebo side of inflammatory changes going on in the body - having an evening or morning ritual of gratitude for what was good or experiential, and letting go of pain and bitterness of the day, may have significant health benefits for us by leaving the body with more positive messages scooting around the body or cells in the form of exosomes or microRNA. It is good advice to try to not go to sleep with an unresolved argument looming overhead. Even a simple agreement to talk about it another time might leave a bit of resolution before trying to sleep. (10)

Our bodies are amazing - sense of smell and sight are somewhat linked wit time perception - is there an odor? Vision activity increases - we may need to scan the environment quickly, for danger, or it may be a tasty food animal to try to catch for dinner. (11)

Nature is also amazing, providing us many beneficial plants around the world.

A tropical flower, the Ylang-ylang (Cananga odorata), has a fragrant essential oil used in perfumes, and it can have healing benefits. Ylang-ylang essential oil may be used topically, diluted in a carrier oil, or diffused in the air. It may have soothing benefits for anxiety and help with sleep. The flowers are dried and powdered for an anti-malarial treatment, or made into a paste and inhaled for asthma.

Name : Cananga odorata Family : Anonaceae വീട്ടിൽ വളർത്തുന്ന ഈ ചെറുവൃക്ഷത്തിൽ സുഗന്ധമുള്ള പുക്കളുണ്ടാവുന്ന, By Ks.mini - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18695454

Disclaimer: This information is being shared within the guidelines of Fair Use for educational purposes. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

  1. Anne Mobergslien, Mouldy Sioud. Exosome-Derived miRNAs and Cellular miRNAs Activate Innate Immunity. J Innate Immun 2014;6:105–110, DOI: 10.1159/000351460 https://www.karger.com/Article/Pdf/351460

  2. Ilbay O, Ambros V. Pheromones and Nutritional Signals Regulate the Developmental Reliance on let-7 Family MicroRNAs in C. elegans. Curr Biol. 2019 Jun 3;29(11):1735-1745.e4. doi: 10.1016/j.cub.2019.04.034. Epub 2019 May 16. PMID: 31104929; PMCID: PMC7245018. https://pubmed.ncbi.nlm.nih.gov/31104929/

  3. Nakamura, K., Sawada, K., Yoshimura, A. et al. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 15, 48 (2016). https://doi.org/10.1186/s12943-016-0536-0 https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-016-0536-0

  4. O'Brien Jacob, Hayder Heyam, Zayed Yara, Peng Chun. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in Endocrinology , 9;2018, pp402 DOI=10.3389/fendo.2018.00402, https://www.frontiersin.org/articles/10.3389/fendo.2018.00402/full

  5. Ylang Ylang Essential Oil Uses and Benefits, healthline.com https://www.healthline.com/health/ylang-ylang#uses

  6. Eleen Y. Shum, Josh L. Espinoza, Madhuvanthi Ramaiah, Miles F. Wilkinson, Identification of novel post-transcriptional features in olfactory receptor family mRNAs, Nucleic Acids Research, Volume 43, Issue 19, 30 October 2015, Pages 9314–9326, https://doi.org/10.1093/nar/gkv324 https://academic.oup.com/nar/article/43/19/9314/2528168

  7. Sarah Kurtenbach, Wen Ding, Garrett M. Goss, et al., Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium. PLoS ONE, November 6, 2017, https://doi.org/10.1371/journal.pone.0187576, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187576

  8. Dexheimer Philipp J., Cochella Luisa. MicroRNAs: From Mechanism to Organism. Frontiers in Cell and Developmental Biology , 8;2020, pp409, DOI=10.3389/fcell.2020.00409 https://www.frontiersin.org/articles/10.3389/fcell.2020.00409/full

  9. Dakota D Witzel, MS, Robert S Stawski, PhD, Resolution Status and Age as Moderators for Interpersonal Everyday Stress and Stressor-Related Affect, The Journals of Gerontology: Series B, 2021;, gbab006, https://doi.org/10.1093/geronb/gbab006 https://academic.oup.com/psychsocgerontology/advance-article-abstract/doi/10.1093/geronb/gbab006/6076809

  10. Chris Melore, If you want to live a longer, healthier life, never go to sleep on an argument. March 26, 2021, https://www.studyfinds.org/longer-life-going-to-sleep-on-arguments/

  11. Zhou B, Feng G, Chen W, Zhou W. Olfaction Warps Visual Time Perception. Cereb Cortex. 2018 May 1;28(5):1718-1728. doi: 10.1093/cercor/bhx068. PMID: 28334302. https://pubmed.ncbi.nlm.nih.gov/28334302/

Other References about Pheromones: