Thymulin (Zn-FTS) is a peptide of nine amino acids (pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn). It is released by reticulo-epithelial (surface-lining tissue) cells of the thymus (an immune gland in the chest) and works as a thymic hormone that T lymphocytes (a type of white blood cell) need to develop and mature. 5Source 5Biochemical characterisation of a serum thymic factorBach JF, Dardenne M, Pleau JM, Rosa J · 19778Source 8The thymus-neuroendocrine axis: physiology, molecular biology, and therapeutic potential of the thymic peptide thymulinReggiani PC, Morel GR, Console GM, Barbeito CG, Rodriguez SS, Brown OA, Bellini MJ, Pleau JM, Dardenne M, Goya RG · 2009 The zinc cofactor (Zn2+, a zinc ion the peptide needs) is built into thymulin's active site and is essential for its 3D shape and for binding to its receptors (docking points on cells). 6Source 6Role of zinc and other metals in the biological activity of the serum thymic factor (thymulin)Dardenne M, Pleau JM, Lefrancier P, Bach JF · 19818Source 8The thymus-neuroendocrine axis: physiology, molecular biology, and therapeutic potential of the thymic peptide thymulinReggiani PC, Morel GR, Console GM, Barbeito CG, Rodriguez SS, Brown OA, Bellini MJ, Pleau JM, Dardenne M, Goya RG · 2009 How it works: (1) T cell maturation: Thymulin helps immature thymocytes (young immune cells) turn into mature T cells by signaling through specific receptors on the cell surface. It increases both CD4+ helper T cells and CD8+ suppressor/cytotoxic T cells (which hold back or kill harmful cells); 7Source 7Thymulin, a zinc-dependent hormoneBach JF, Dardenne M · 1989 (2) Anti-inflammatory signaling: Thymulin blocks activation of NF-κB (a master switch for inflammation), lowers production of the inflammation signals IL-6, TNF-α, and IL-8, and reduces phosphorylation of p38 MAPK (the chemical tagging that switches on an inflammation-related enzyme); 14Source 14Immunomodulatory role of thymulin in lung diseasesSantos M, Henriques-Coelho T, Leite-Moreira A · 201015Source 15Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathwaysNasseri B, Zaringhalam J, Daniali S, Manaheji H, Abbasnejad Z, Nazemian V · 201916Source 16Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammationNovoselova EG, Lunin SM, Glushkova OV, Khrenov MO, Parfenyuk SB, Zakharova NM, Fesenko EE · 2018 (3) Immune balance: Thymulin keeps helper and suppressor T cells in proper balance; 7Source 7Thymulin, a zinc-dependent hormoneBach JF, Dardenne M · 198912Source 12Serum thymulin in human zinc deficiencyPrasad AS, Meftah S, Abdallah J, Kaplan J, Brewer GJ, Bach JF, Dardenne M · 1988 when this balance is lost, it contributes to immunodeficiency (a weak immune system) and autoimmunity (the immune system attacking the body); (4) Brain protection: Microglia (immune cells of the brain and spinal cord) respond to thymulin and reduce the brain inflammation caused by endotoxin (a bacterial toxin) by blocking NF-κB; 15Source 15Thymulin treatment attenuates inflammatory pain by modulating spinal cellular and molecular signaling pathwaysNasseri B, Zaringhalam J, Daniali S, Manaheji H, Abbasnejad Z, Nazemian V · 201917Source 17Thymulin related peptide attenuates inflammation in the brain induced by intracerebroventricular endotoxin injectionSafieh-Garabedian B, Jabbur SJ, Dardenne M, Saade NE · 201118Source 18Role of thymulin or its analogue as a new analgesic moleculeDardenne M, Saade N, Safieh-Garabedian B · 2006 (5) Aging: Thymulin levels fall with age (about 50% lower by age 60), which adds to immune senescence (the immune system wearing down with age). Restoring thymulin can reverse age-related thymic involution (shrinking of the thymus). 9Source 9Age, thymic involution, and circulating thymic hormone activityLewis VM, Twomey JJ, Bealmear P, Goldstein G, Good RA · 197811Source 11Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old miceMocchegiani E, Santarelli L, Muzzioli M, Fabris N · 1995 Zinc deficiency lowers the amount of active thymulin even when the thymus makes normal amounts, 11Source 11Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old miceMocchegiani E, Santarelli L, Muzzioli M, Fabris N · 199512Source 12Serum thymulin in human zinc deficiencyPrasad AS, Meftah S, Abdallah J, Kaplan J, Brewer GJ, Bach JF, Dardenne M · 1988 so taking zinc along with it is critical for it to work.