Cell Senescence and Herxheimer Reactions

Cell Senescence and Herxheimer Reactions

Our bodies are an intelligent ecosystem, constantly repairing and regrowing cells in an effort to maintain and restore our health. Part of the regular cellular process is called cell senescence and it happens when cells that should die off and be replaced by new ones refuse to do so. Instead, they stay ensconced in our body and create mitochondrial dysfunction which leads to inflammation. These cells not only overstay their welcome, but they create a harmful byproduct called senescence-messaging secretome (SASP). This complex mixture includes “proinflammatory cytokines, chemokines, growth factors, and proteases” (McHugh & Gil, 2018). SASP has been shown to “recruit inflammatory cells, remodel the extra-cellular matrix, trigger unwanted cell death, induce fibrosis, and inhibit cell function” (Seeds, 2020). While this effect seems deleterious to our health, cell senescence has both positive and negative implications. The difference of whether it is beneficial or harmful depends on the length of time that cellular senescence occurs in the body.

Research has shown that transient senescent cells which stay for a short amount of time are helpful, while lingering senescence cells who overstay their use are harmful. The beneficial biological functions include “regulation of embryonic development, wound healing, resolution of fibrosis and tumor suppression” (Huang, Hickson & Eirin, 2022). However the negative impacts are many and include advanced aging as well as influencing the pathogenesis of “chronic diseases, including osteoporosis, metabolic syndrome, type 2 diabetes mellitus, cancer, reproductive aging, atherosclerosis, neurodegeneration, glaucoma, chronic kidney disease tumor development, chronic inflammation, immune deficit and stem cell exhaustion. (Huang, Hickson & Eirin, 2022). Cellular senescence has a compounding effect, which adds to the harm that it can do in the body. This is because an individual cell will affect nearby cells as well as distant tissues with a cascading inflammatory response. The natural process of cell senescence increases gradually as we age, but can also be triggered by stress, poor diet, overfeeding, high blood glucose, lack of exercise, or even medication.

For patients with Lyme Disease or other conditions due to spirochetes, a group of spiral-shaped bacteria, a similar reaction can occur when they are treated with antibiotics. This phenomenon is called a Jarisch Herxheimer reaction (JHR) and symptoms include “fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of skin lesions” (Dhakal & Sbar, 2022). The reason for this reaction is similar to cell senescence, as it is due to the presence of pro-inflammatory cytokines. Cytokines are a type of secreted protein that can be pro-inflammatory or anti-inflammatory and affect cell communication. Pro-inflammatory cytokines are helpful to the body in moderation, as they bring more white blood cells to injuries or infection and assist in healing.

In excess, they are harmful rather than helpful. This is what happens when a person experiences a Jarisch Herxheimer reaction. Pro-inflammatory cytokines are released by white blood cells when the body sees the toxins or germs being destroyed by the herbal or prescription antibiotics. As the spirochetes are dying off, more cytokines are made which worsens symptoms. Sometimes, this is misdiagnosed as an allergic reaction instead of the transient clinical reaction that it is. While symptoms from a Jarisch Herxheimer reaction are usually not serious and resolve within 24-hours, there are rare cases when they can cause serious complications.

In both cell senescence and Herxheimer reactions, pro-inflammatory cytokines are a major cause of adverse reactions. One way to mediate them is via intravenous (IV) therapy. This type of treatment delivers medication directly to the circulatory system so treatments can retain their potency and effectiveness. An excellent IV therapy for clinical manifestations due to pro-inflammatory cytokines is glutathione, which is a naturally-occurring tripeptide enzyme made up of cysteine, glycine, and glutamic acid. Not only is it anti-cytotoxic, but it neutralizes free radicals, helps create antioxidants, regulates cellular proliferation and apoptosis, and is essential to mitochondrial function.  By adding additional glutathione intravenously, the body’s white blood cells are given assistance in combating cellular dysregulation and pro-inflammatory cytokines. Other IV treatments such as Alpha Lipoic Acid (ALA) and certain peptides can also be used as treatment. If you would like to learn more, please schedule a meeting with us to discuss what would work best for you.


Dhakal A, Sbar E. (2022). Jarisch Herxheimer Reaction. (2022). Treasure Island, FL: StatPearls.

Huang, W., Hickson, L.J., Eirin, A. et al. Cellular senescence: the good, the bad and the unknown. Nat Rev Nephrol 18, 611–627 (2022).

Kim, E. C., & Kim, J. R. (2019). Senotherapeutics: emerging strategy for healthy aging and age-related disease. BMB reports, 52(1), 47–55.

McHugh, D., & Gil, J. (2018). Senescence and aging: Causes, consequences, and therapeutic avenues. The Journal of cell biology, 217(1), 65–77.

Pizzorno J. (2014). Glutathione!. Integrative medicine (Encinitas, Calif.), 13(1), 8–12.

Seeds, W. A. (2020). The peptide protocols: A handbook for practitioners. Spire Institute.

Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37.

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Medically reviewed by Dr. Stephen Matta, DO, MBA CAQSM and Mary Anne Matta, MS, MA, LAC

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