Cytokine Therapy: Biohacking Cell Communication for Aging

What are Cytokines?

Cytokines: small secreted proteins released by cells that have a specific effect on the interactions and communications between cells.

Cytokines, from the Greek cyto meaning “cell” and kinos meaning “movement”, are tiny protein molecules secreted by cells that communicate with other cells. Cytokines may be classified as peptides, proteins, exosomes, secretomes or glycoproteins. Sophisticated and profound complexes of cytokines found in our bodies are involved in cellular communications. They are nano-sized molecules working as cross-cell messengers and channels. It might help to think of cytokines as the body’s mobile phone system.

The Functions of Cytokines in Aging

A crucial component of how well we age is related to the levels of inflammation in the body. Although inflammation is a natural and healthy response, prolonged elevated levels become disastrous for the body, linked to chronic diseases, and accelerated aging. This interconnected link has given rise to a new term, ‘inflamm-aging’. Although research is still elucidating the exact mechanisms of “inflamm-aging”, a common finding involves an imbalance of cytokines. [1]

Cytokines communicate with both near and far cells in the following three ways:
1. Autocrine action: affecting only the cell from which it was secreted
2. Paracrine action: affecting only neighbouring cells
3. Endocrine action: allowing hormones to affect cells in a distant area through the blood circulation

Cytokine Therapy For Anti-Aging

Cytokines can be the difference between the body’s success and failure. An imbalance of cytokines is at the root of most diseases as the cells are either lacking the correct signals to keep healthy, or are receiving the wrong signals. Cytokine therapy involves administering external cytokines to the body. It is one of the new exciting fields in medicine which, like stem cells, could dramatically change the face of medicine and treatment protocols to support a variety of conditions.

1. Reduced inflammation [2-4]
Inflammation is at the root of all chronic diseases. As messenger molecules, cytokines can either be pro-inflammatory (IL-1, TNF-α) or anti-inflammatory (IL-4, IL-6). Blocking pro-inflammatory cytokine levels with their antagonists is an effective and highly selective method for reducing inflammation.

2. Improved skin appearance [5]
Cytokines play a key role in the aging process of the skin, including loss of collagen, increase in skin infections, compromised wound-healing, and dry, wrinkled texture. With cytokine therapy, these signaling pathways can be targeted to improve the function, integrity, and appearance of our skin.

3. Improved immune system regulation
When the body encounters an infection, cytokines are secreted from our immune cells and rush to the site to signal for help. This reaction is called a ‘cytokine storm’ and creates a localized site of inflammation and immune activity to deal with the invader. Cytokines are vital players in our immune regulation and can be harnessed for their potential therapeutic effects for cancer [6] and autoimmune diseases [7,8] like inflammatory bowel disease, psoriasis, and rheumatoid arthritis.

4. Prevent cognitive decline
Research has shown that the levels of individual cytokines can affect learning, memory, and synaptic plasticity. One of the targeted pathways is through modulating brain inflammation [9], which has disastrous effects on brain function and cognitive degeneration. We also see a casual link between cytokine deregulation and the progression of brain diseases like Alzheimer’s disease. [10]

5. Pain reduction [11]
As we age, aches and pains become a common complaint. Cytokines are largely to blame for daily pains, whether from joints, bones, or muscles. Research has shown that cytokine crosstalk between immune, glial, and neural cells is integral to the development of pain symptoms and targeting these pathways to manipulate cytokine interactions can be a successful strategy to manage inflammation and pain.

6. Improved weight management
Cytokines have been studied for their effects on weight management and metabolism. One of particular note is IL-18, which was shown to modulate food intake, metabolism, and body fat levels in rats. [12] Later studies have utilized this role of cytokines to improve weight loss and increase insulin sensitivity in human trials. [13]

References:

  1. Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol. 2018;9:586. doi:10.3389/fimmu.2018.00586
  2. Donnelly RP, Young HA, Rosenberg AS. An overview of cytokines and cytokine antagonists as therapeutic agents. Ann N Y Acad Sci. 2009;1182:1‐13. doi:10.1111/j.1749-6632.2009.05382.x
  3. Kopf, M., Bachmann, M. & Marsland, B. Averting inflammation by targeting the cytokine environment. Nat Rev Drug Discov. 2010;9:703–718. doi.org/10.1038/nrd2805
  4. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45(2):27‐37. doi:10.1097/AIA.0b013e318034194e
  5. Borg M, Brincat S, Camilleri G, Schembri-Wismayer P, Brincat M, Calleja-Agius J. The role of cytokines in skin aging. Climacteric. 2013;16(5):514-521. doi:10.3109/13697137.2013.802303
  6. Ardolino, Michele et al. Cytokine treatment in cancer immunotherapy. Oncotarget. 2015;6(23):19346-7. doi:10.18632/oncotarget.5095
  7. Astrakhantseva, I.V., Efimov, G.A., Drutskaya, M.S. et al. Modern anti-cytokine therapy of autoimmune diseases. Biochemistry Moscow. 2014;79:1308–1321. https://doi.org/10.1134/S0006297914120049
  8. Qingdong Guan, Xiaoling Gao, Junhui Wang, Yu Sun, and Sudhanshu Shekhar. Cytokines in Autoimmune Disease. Mediators of Inflammation. 2017. doi.org/10.1155/2017/5089815
  9. Donzis EJ, Tronson NC. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences. Neurobiol Learn Mem. 2014;115:68‐77. doi:10.1016/j.nlm.2014.08.008
  10. Azodi S, Jacobson S. Cytokine Therapies in Neurological Disease. Neurotherapeutics. 2016;13(3):555‐561. doi:10.1007/s13311-016-0455-1
  11. Vanderwall Arden G. and Milligan Erin D. Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management. Frontiers in Immunology. 2019;10:3009. doi:10.3389/fimmu.2019.03009
  12. Zorrilla EP, Sanchez-Alavez M, Sugama S, et al. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci USA. 2007;104(26):11097‐11102. doi:10.1073/pnas.0611523104
  13. Weiss EP, Reeds DN, Ezekiel UR, Albert SG, Villareal DT. Circulating cytokines as determinants of weight loss-induced improvements in insulin sensitivity. Endocrine. 2017;55(1):153‐164. doi:10.1007/s12020-016-1093-4
Rachel

Rachel Erwin, Nutritionist & Content Writer

Rachel is a Nutritionist with a BSc in Biology and Global Health from the University of Toronto, and a Postgraduate Diploma in Human Nutrition from the University of Ulster. She has counselled and educated clients in Hong Kong, whose health goals ranged from weight loss to detox and hormone balancing. Her love of writing led her to complete ‘Writing in the Sciences’, offered by Stanford University, and since then she has contributed several evidence-based health articles to various publications.

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