Acupuncture Epigenomics

Michael D. Beys D.Ac.C.M., L.Ac.

Abstract:

Currently  many effects of acupuncture can be explained in terms of endogenous physiological mechanisms, and  these effects are reported as similar or sometimes superior to established treatments with a very low incidence of side effects (Lund, 2016).  One such mechanism is acupuncture-sirtuin-epigenetic modification. We hope to demonstrate how acupuncture’s release of sirtuins is used therapeutically to treat disease and for prevention by improving cellular health and delaying apoptosis.

 

Introduction.

There is no argument that acupuncture has been around for a long time.  The Huang Di Nei Jing states that humans are microcosm within a macrocosm.  If we take the cellular model, trillions of cells work together to allow for a human to thrive.  But as humans have life a cycle so do cells. Each cell is programmed to function by its genetic code and apoptosis (cell death) is programmed into it.  Just as environment impacts the health of humans so does it affect the genetic code of cells. Research indicates an epigenomic mechanism for acupuncture and this article aims to explain its impact on the epigenome.

 

Epigenetics, Epigenomics, and Cell Apoptosis.

DNA in the nucleus provides a code on how cell perform.  Epigenetics is the study of the on/off switches of how genes are expressed in relation to cellular function.  Epigenomics is the study of how those switches biochemically turn on and off. There are many factors that turn these switched on and off.  Chemical and environmental factors like diet, air, and water quality are most apparent but also emotional factors like nurturing play an important role (Enriquez, J. p.166).  For the purpose of this article we will explore the mechanical effects of acupuncture and how certain substances are released in order to turn on/off these genetic switches (up/down-regulate gene expression).

Genomics is an approach to collecting information from genomes to guide medical decision making and to tailor strategies for each patient. Individual transcriptional profiles of patients have been mined to search for target molecules of acupuncture treatments. Candidate genes or pathways associated with the protective effect of acupuncture treatments have been revealed through genomic analysis for several diseases and symptoms (Lin, 2012). Furthermore, studies suggest that acupuncture suppresses cell apoptosis.  Research confirms that acupuncture induces the activation of SIRT1 through acupuncture-SIRT1-epigenetic modification (Luo, 2017). Acupuncture may also act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2 pathway. (Wang, 2014)

 

Sirtuins

What are sirtuins?  Sirtuins have been clearly shown to be as a class of proteins; expressed by SIRT genes 1-7.  They regulate many cellular processes and play important functions in diverse tissues and organ systems. Sirtuin functions have been described in the central/peripheral nervous system, cardiovascular system, immune system, liver, bone, skeletal muscles, stem cells, and tissue regeneration. They have also been associated with most major diseases, such as cardiovascular diseases, cancer, metabolic disorders, neurodegenerative diseases, arthritis, and osteoporosis, all of which are age-related (Dang, 2014). Sirtuins have been implicated in influencing a wide range of cellular processes like aging, transcription, apoptosis, inflammation (Preyat, 2013), and stress resistance, as well as energy efficiency and alertness during low-calorie situations (Satoh, 2010).

Acupuncture-Sirtuin-epigenetic modification.

Currently there have only been studies of acupuncture acting on SIRT 1 and 2 genes that express sirtuin 1 and sirtuin 2 protein.

The local endogenous physiological effect of acupuncture represents the impact of microinjury on local tissue.  Substance P and Calcitonin gene-related peptide increase circulation through vasodilation (Wu, 2015). Another local endogenous mechanism observed:

  1. Electroacupuncture on stomach 36 point increases the production of Nitrous Oxide (NO) in arterioles, and  increases the expression of endothelial Nitrous oxide synthase (eNOS) and neuronal nitrous oxide synthase (nNOS) (Kim, 2006)
  2. production of NO by Calorie restriction, or in this case electroacupuncture, switches on SIRT1 gene expression and eNOS has been implicated in regulation of the expression of Sirtuin 1(Nisoli, 2005).
  3. Switching on SIRT 1 gene expression through electroacupuncture:

When the micro injury signal gets to the brain it releases endorphins (Han, 2005), also within the central nervous system:

  1. Micro RNA (miRNA) assay has confirmed that miRNA-339 was upregulated in the medulla of Spontaneously Hypertensive Rats treated with manual acupuncture at liver 3 acupuncture point.  miRNAs play an important role in the antihypertensive activity of acupuncture therapy (Wang, 2015).
  2. miR-339 switches off SIRT 2 gene expression in human and rat neurons. Since Sirtuin 2 plays a critical role in multiple important cellular functions (Wang, 2015)…
  3. Down-regulating Sirtuin 2 switches on its targets such as NF-κB and FOXO1, the data implies that acupuncture may act through epigenetic changes (Wang, 2015).

Content footnote:

PCG-1α:  Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

NF-κB:  nuclear factor kappa-light-chain-enhancer of activated B cells

FOXO1: Forkhead box protein O1

are proteins expressed by their corresponding genes.  For further clarification please reference their effect on physiology.

A word on mice

The mouse model is used often time because it is a stepping stone to RCTs.  Because acupuncture is so safe it skipped this preliminary stage of testing and went straight to RCTs.  It is unethical to induce disease on humans and oftentimes tissue is analyzed posthumously. The benefit is that animals, immune to placebo (Sedita, 2015), lead to a true physiological model.  Which could lead to RCT’s. As far as physiology, mice and humans share virtually the same set of genes. Almost every gene found in one species so far has been found in a closely related form in the other. Of the approximately 4,000 genes that have been studied, less than 10 are found in one species but not in the other.   Mouse models also afford the opportunity to test possible therapeutic agents and evaluate their precise effects (genome.gov, 2010), in this case acupuncture. The difference lies in how we look rather than how our cells operate and organs function.

Conclusion

Acupuncture epigenomically switches on/off gene expression of sirtuins 1 and 2 which further switch on/off certain gene expressions that could epigenetically impact cellular function.  Based on the biological and immunological results in 40 studies, acupuncture could modulate cell apoptosis to reduce cell death in different pathological states (Luo, 2017). As indicated above acupuncture-NO/eNOS-sirtuin-epigenetic modification is a pathway that leads cellular health.

If humans are a microcosm within a macrocosm then that cosmos is comprised of cells.  Trillions of cells operate on a blueprint that is the genome. As adults we lose 30-50 billions cells to apoptosis daily.  If acupuncture can modulate apoptosis through an epigenetic mechanism then we can improve cellular function and delay or prevent cell death.

In closing, Genomic testing is a powerful tool in the early detection of all disease besides colon and breast cancer.  Genomics plays a role in 9 of the 10 leading causes of death (Why Genomics is Important, helthypeople.gov). If we could find the disease early then we could prevent it through the epigenome.  If using the application of acupuncture as a medicine then using it for prevention is a science the acupuncture community ought to look into. In a medical system transitioning to one of prevention (Shi, p. 44) acupuncture should be at the forefront.

 

About the author

Michael D. Beys L. Ac., D.A.C.Mc,  is a graduate of Pacific college of Oriental Medicine. His training consisted of over 3000 hours in the study of acupuncture and herbal medicine.  He was supervising acupuncturist at RUMC’s substance abuse Detox Center and South Beach Psychiatric Rehab facility.

He is also fluent in Greek, and Spanish, and proficient in mandarin, Arabic, and Italian.   Currently his practice focuses on fertility and women’s health, pain management, and substance abuse mental health.

 

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