Microstructure of lymphoid tissue in lymph nodes of different localization in young, mature and old rats

Document Type : Research Paper

Authors

1 Laboratory of Physiology Lymphatic System, Institute of Genetics and Physiology SC MSHE RK, 050060 Almaty, Kazakhstan

2 Kazakh National University, al -Farabi, Almaty, Kazakhstan

3 Novosibirsk State University, Novosibirsk, Russia

10.22124/cjes.2025.9213

Abstract

Aging is a natural biological process of gradual degradation of parts and systems of the human body and the consequences of this process. These changes occur in the human genotype, both under the influence of environmental factors and as a result of endogenous processes, namely, a deficiency of antioxidant enzymes, changes in the immune system and the development of chronic inflammation. The lymphatic system is the internal environment of the body. In recent years, we and other scientists have determined general and regional signs of aging of the lymphatic system, reflecting a decrease in drainage-detoxification and immune functions, caused by a deficiency of trace elements in the lymph nodes. Considering the important role of the lymphatic system in the body, its participation in tissue drainage and its compensatory and adaptive functions, it is of interest to develop a program of restorative methods of lymphatic system functions on the processes occurring in the aging organism, and thereby contribute to the prolongation of life. This study aimed to determine the ratio of functional zones and microstructures of lymphoid tissue in nodes of different locations in young, mature, and senile rats. Lymph nodes were analyzed using Avtandilov's morphometry, and the samples were fixed in 10% neutral buffered solution formalin or Telesnitsky's fluid, processed, and embedded in paraffin for histological sectioning with various dyes, including hematoxylin and eosin. This study presents data on aging affects the lymph node microstructure and functional area. In young and mature animals, no significant differences were observed. However, aging leads to thickening of the capsule and increased connective tissue around blood vessels, disrupting the lymphoid lobule structure and causing lymph drainage issues. In older animals, the medulla remains unchanged as long as lymph flow is maintained. Compared to younger animals, older ones showed more connective tissue and fewer lymphoid nodules. There is a decreased in certain immune cell types, indicating lower immunoreactivity. Conclusion: In young animals, no significant changes were observed compared to mature animals. Ageing in lymph nodes showed increased connective tissue and reduced lymphoid nodules, with a decrease in certain cell types, and an elevation in the number of reticular cells, indicating lower immunoreactivity.

Keywords

References

Xiong, R, Shan, S, Wang, X, Zhang, X, Yu, H, Shi, H & Wang, X 2020, Aloperine attenuates carbon tetrachloride-induced mouse hepatic injury via Nrf2/HO-1 pathway. Tropical Journal of Pharmaceutical Research, 19: 983-988.
Yeh, YH, Hsieh, YL & Lee, YT 2013, Effects of yam peel extract against carbon tetrachloride-induced hepatotoxicity in rats. Journal of Agricultural and Food Chemistry, 61: 7387-7396. Åberg, E, Kukkonen, I & Sarpila, O 2020, From double to triple standards of ageing. Perceptions of physical appearance at the intersections of age, gender and class. Journal of Aging Studies, 55: 100876, DOI: 10.1016/j.jaging.2020.100876.
Abdreshov, SN, Akhmetbaeva, NA, Atanbaeva, GK, Mamataeva, AT & Nauryzbai, UB 2019, Adrenergic innervation of the thyroid gland, blood and lymph vessels, and lymph nodes in hypothyroidism. Bulletin of Experimental Biology and Medicine, 168: 295-299, DOI: https://doi.org/10.1007/s10517-019-04694-8.
Abdreshov, SN, Demchenko, GA, Yeshmukhanbet, AN, Yessenova, MA, Mankibaeva, SA, Atanbaeva, GK & Kulbayeva, MS 2024, Morphofunctional alteration of mesenteric lymph nodes in the inflammation of the abdominal cavity. Biology, 13: 166, DOI: 10.3390/biology13030166.
Abdreshov, S, Kozhaniyazova, U, Bgatova, N, Demchenko, G, Shynybekova, Sh & Oxikbayev, B 2023, Morphofunctional state and microstructure of regional lymph nodes in experimental hypothyroidism and under correction. ArchivEuroMedica, 1: 6, e1. DOI: htpp://dx.doi. org/10.35630/2023/13/6.601.
Ahmadi, O, McCall, JL & Stringer, MD 2013, Does senescence affect lymph node number and morphology? A systematic review. ANZ Journal of Surgery, 83: 612-618, DOI: https://doi.org/10.1111/ans.12067
Ancaster, JN 2023, Aging of lymphoid stromal architecture impacts immune responses. Seminars in Immunology, 70: 101817, DOI: 10.1016/j.smim.2023.101817.
Andreollo, NA, Santos, EF, Araújo, MR & Lopes, LR 2012, Rat’s age versus human’s age: What is the relationship? Arquivos Brasileiros De Cirurgia Digestiva, 25: 49-51.
Avtandilov, GG 1990, Medical morphometry. Moscow, Medicine.
Beregi, E, Biró, J & Regius, O 1980, Age-related morphological changes in lymphocytes as a model of aging. Mechanisms of Ageing and Development, 14: 173-180, DOI: 10.1016/0047-6374(80)90116-5.
Betterman, KL & Harvey, NL 2016, The lymphatic vasculature: Development and role in shaping immunity. Immunological Reviews, 271: 276-292, DOI:10.1111/imr.12413.
Bontumasi, N, Jacobson, JA, Caoili, E, Brandon, C, Kim, SM & Jamadar, D 2014, Inguinal lymph nodes: Size, number, and other characteristics in asymptomatic patients by CT. Surgical and Radiologic Anatomy, 36: 1051-1055, DOI: 10.1007/s00276-014-1255-0.
Budamagunta, V, Foster, TC & Zhou, D 2021, Cellular senescence in lymphoid organs and immunosenescence. Aging (Albany NY), 13(15): 19920–19941, DOI: 10.18632/aging.203405.
Cakala-Jakimowicz, M, Kolodziej-Wojnar, P & Puzianowska-Kuznicka, M 2021, Aging-related cellular, structural and functional changes in the lymph nodes: A significant component of immunosenescence? An overview. Cells, 10: 3148, DOI: https:/ /doi.org/10.3390/cells10113148.
Chen, Y, He, X,Cai, Ji & Li, Q 2024, Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases. Journal of Biomedical Research, 38(3): 206-221, DOI: 10.7555/JBR. 37.20230264.
Chinn, IK, Blackburn, CC, Manley, NR & Sempowski, GD 2012, Changes in primary lymphoid organs with aging. Seminars in Immunology, 24:309-320, DOI: 10.1016/j.smim.2012.04.005.
Demchenko, GA, Abdreshov, SN, Akhmetbaeva, NA, Makashev, EK, Nurmakhanova, BA, Balkhybekova AO & Kalekeshov, AM 2021, The specifics of adrenergic innervation of lymph nodes from different body regions in young, mature and old animals. Bulletin of Experimental Biology and Medicine, 170: 283-287, DOI: https://doi.org/10.1007/s10517-021-05052-3.
Demchenko, GA, Abdreshov, SN & Nurmakhanova, BA 2019, Contractile activity of Lymph Nodes in young, middle-aged, and old rats. Bulletin of Experimental Biology and Medicine, 167:194–197, DOI: https://doi.org/10.1007/s10517-019-04489-x.
Demchenko, GA, Nurmakhanova, BA, Abdreshov, SN, Koibasova, LU, Zhunussova, GS & Imankulova, SK 2023, Phytocorrection of age-related changes in the composition of blood plasma, lymph, and interstitial fluid. Bulletin of Experimental Biology and Medicine, 175: 785-790, DOI: https://doi.org/10.1007/s10517-023-05947-3.
Denic, A, Glascock, RJ, Rule & AD 2016, Structural and functional changes with the aging kidney. Advances in Chronic Kidney Disease, 23: 19-28. DOI: 10.1053/j.ackd.2015.08.004.
Fletcher, AL, Acton, SE, Knoblich, K 2015, Lymph node fibroblastic reticular cells in health and disease. Nature Reviews Immunology, 15: 350-361, DOI:10.1038/nri3846.
Garcia-Dominguez, M 2025, Pathological and inflammatory consequences of aging. Biomolecules, 15: 404, DOI: https://doi.org/10.3390/biom15030404
Hadamitzky, C, Spohr, H, Debertin, A, Guddat, S, Tsokos, M & Pabst, R 2010, Age-dependent histoarchitectural changes in human lymph nodes: An underestimated process with clinical relevance? Journal of Anatomy, 216: 556-562, DOI: 10.1111/j.1469-7580.2010.01213. x.
Hagen, M & Derudder, E 2020, Inflammation and the alteration of B-cell physiology in aging. Gerontology, 66: 105–113, DOI: https://doi.org/10.1159/000501963.
Ham, AW, Cormack, DH 1979, Histology. 8th edition. Philadelphia Toronto: Lippincott Co.
Harinath, G, Zalzala, S, Nyquist, A, Wouters, M, Isman, A, et al. 2024, Role of quality of life data as an endpoint for collecting real-world evidence within geroscience clinical trials. Aging Research Reviews, 97:102293, DOI: 10.1016/j.arr.2024.102293.
Hsu, MC & Itkin, M 2016, Lymphatic anatomy. Techniques in Vascular and Interventional Radiology, 19: 247-254, DOI: 0.1053/j.tvir.2016.10.003.
Hu, C, Zhang, X, Feng, T, Ma, ZG, Tang, QZ 2022, Cellular senescence in cardiovascular diseases: A systematic review. Aging Disability, 13: 103-128.
Imprint of Elsevier: London, UK; San Diego, CA, USA, 728 p.
Jakica, B, Kerjaschki, D & Wicka, G 2020, Lymphatic capillaries in aging. Gerontology, 66: 419–426, DOI: 10.1159/000508459.
Johnson, LA 2021, In sickness and in health: The immunological roles of the lymphatic system. International Journal of Molecular Sciences, 22: 4458, DOI: https://doi.org/10.3390/ijms22094458.
Kataru, RP, Park, HJ, Shin, J, Baik, JE, Sarker, A, Brown, S & Mehrara, BJ 2022, Structural and functional changes in lymphatic vessels aged skin. Frontiers in Aging, 3: 864860, DOI: 10.3389/fragi.2022.864860
Koubasova, L, Parmanbekova, M & Abdreshov, S 2014, Effects of toxic hepatitis on the lymphatic system and its correction. Journal of Biotechnology, 185: 100, DOI: 10.1016/j.jbiotec.2014.07.340.
Krupina, KM, Petrash, MD, Golubitskaya, DI & Strizhitskaya, Oyu 2024, Peculiarities of perceiving aging by men and women during the middle and late adulthood periods.  Izvestiya Saratov University. Acmeology of Education. Developmental Psychology, 13(49): 60-70, DOI:10.18500/2304-9790-2024-13-1-60-70
Laribi, K, Lemaire, P, Sandrini, J, de Materre, A 2017, Baugier Advances in the understanding and management of T-cell prolymphocytic leukemia. Oncotarget, 8(61): 104664-104686, DOI:10.18632/ oncotarget.22272.
Lee, J & Kim, HJ 2022, Normal aging induces changes in the brain and neurodegeneration progress: Review of the structural, biochemical, metabolic, cellular, and molecular changes. Frontiers in Cellular Neuroscience, 14: 931536.
Li, G, Cao, Y, Tang, X, Huang, J, Cai, L & Zhou, L 2022, The meningeal lymphatic vessels and the glymphatic system: Potential therapeutic targets in neurological disorders. Journal of Cerebral Blood Flow & Metabolism, 42: 1364-1382, DOI: 10.1177/0271678X221098145,
Liao, S & Padera, TP 2013, Lymphatic function and immune regulation in health and disease. Lymphatic Research and Biology, 11:136-143, DOI:10.1089/lrb.2013.0012.
Lobov, GI, Pan’kova, MN & Abdreshov, SN 2015, Transport function of the lymph nodes in young and old animals. Advances in Gerontology, 28: 681-686.
Maiborodin, IV, Agzaev, MK, Ragimova, TM & Maiborodin, II 2016, Age-related changes in the structure of lymphoid organs: A literature review. Advances in Gerontology, 6: 282-290, DOI: https://doi.org/10.1134/S2079057016040081.
Martinez-Cue, C & Rueda, N 2020, Cellular Senescence in Neurodegenerative Diseases. Frontiers in Cellular Neuroscience, 14:16.
Masters, AR, Hall, A, Bartley, JM, Keilich, SR, Lorenzo, EC, Jellison, ER, Puddington, L & Haynes, L 2019, Assessment of lymph node stromal cells as an underlying factor in age-related immune impairment. Journals of Gerontology: Series A, Biological Sciences and Medical Sciences, 74: 1734–1743, DOI: https://doi.org/10.1093/gerona/glz029.
Merkulov, GA 1969, Course of pathohistological techniques. Leningrad, Med.
Milutinovic, S, Abe, J, Godkin, A, Stein, JV & Gallimore, A 2021, The dual role of high endothelial venules in cancer progression versus immunity. Trends Cancer, 7: 214-225, DOI: 10.1016/j.trecan.2020.10.001.
Morandi, F, Di Carlo, E, Ferrone, S, Petretto, A, Pistoia, V & Airoldi, I 2014, IL-27 in human secondary lymphoid organs attracts myeloid dendritic cells and impairs HLA class I-restricted antigen presentation. Journal of Immunology, 192(6): 2634-2642, DOI: 10.4049/jimmunol.1302656.
Nurmakhanova, B, Demchenko, G, Abdreshov, S, Imankulova, S & Koibasova, L 2023, Adrenergic innervation of thoracic lymphatic duct in postnatal ontogenesis. Translational Medicine of Aging, 7: 133-136, DOI: https://doi.org/10.1016/j.tma.2023.10.00.
Olszewski, WL 2003, The lymphatic system in body homeostasis: Physiological conditions. Lymphatic Research and Biology, 1: 11-21, DOI:10.1089/15396850360495655
Premier, RR & Meeusen, EN 1998, Lymphocyte surface marker and cytokine expression in peripheral and mucosal lymph nodes. Immunology, 94: 363-367, DOI: 10.1046/j.1365-2567.1998.00522.x.
Priya, NS 2023, Lymph nodes in health and disease pathologist's perspective. Journal of Oral and Maxillofacial Pathology, 27: 6-11. DOI: 10.4103/jomfp.jomfp_40_23.
Qi, H, Kastenmuller, W & Germain, R 2014, Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue. Annual Review of Cell and Developmental Biology, 30: 141-167, DOI: 10.1146/annurev-cellbio-100913-013254.
Randall, TD 2010, Bronchus-associated lymphoid tissue (BALT) structure and function. Advances in Immunology, 107: 187–241, DOI: https://doi.org/10.1016/B978-0-12-381300-8.00007-1.
Reid, IM 1980, Morphometric methods in veterinary pathology: A review. Veterinary Pathology, 17: 522-543.
Richner, JM, Gmyrek, GB, Govero, J, Tu, Y, van der Windt, GJ, Metcalf, TU, Haddad, EK, Textor, J, Miller, MJ & Diamond, MS 2015, Age-dependent cell trafficking defects in draining lymph nodes impair adaptive immunity and control of West Nile virus infection. PLOS Pathogens, 11: e1005027, DOI: https://doi.org/10.1371/journal.ppat.1005027.
Rodriguez-Mogeda, C, Koubiyr, I, Prouskas, SE, Georgallidou, M, van der Pol, SMA, Fernandez, RF, de Graaf, YG, van der Werf, YD, Jonkman, LE, Schenk, GJ, Barkhof, F, Hulst, HE, Witte, ME, Schoonheim, MM, de Vries, HE 2025, Thalamic atrophy in multiple sclerosis is associated with tract disconnection and altered microglia. Acta Neuropathologica, 149(1): 52, DOI: 10.1007/s00401-025-02893-4.
Rogers, LF 2006, Magnetic resonance images of reactive lymphadenitis. Lymphology, 39: 53-54.
Rui-Cheng, Ji 2024, The emerging importance of lymphangiogenesis in aging and aging-associated diseases. Mechanisms of Ageing and Development, 221: 111975, DOI: https://doi.org/10.1016/ j.mad.2024.111975
Sackstein, R 1993, Physiologic migration of lymphocytes to lymph nodes following bone marrow transplantation: Role in immune recovery. Seminars in Oncology, 20 (5 Suppl 6): 34-39.
Sengupta, P 2013, The laboratory rat: Relating its age with human’s. International Journal of Preventive Medicine, 4: 624-630.
Shang, T, Liang, J, Kapron, CM & Liu, J 2019, Pathophysiology of aged lymphatic vessels. Aging,  11: 6602-6613, DOI: https://doi.org/10.18632/aging.102213.
Siegrist, CA & Aspinall, R 2009, B-cell responses to vaccination at the extremes of age. Nature Reviews Immunology, 9: 185-194, DOI.org/10.1038/nri2508.
Silva, FFVe, Ballini, A, Di Domenico, M & Padín-Iruegas, ME 2024, The Complexity of the pancreatic lymphatic system and the key role of para-aortic lymph node metastasis in pancreatic cancer prognosis prediction: A comprehensive review. Anatomia, 3: 124-135, DOI: https://doi.org/10.3390/ anatomia3020010.
Stritt, S, Koltowska, K & MЁakinen, T 2021, Homeostatic maintenance of the lymphatic vasculature. Trends in Molecular Medicine, 27: 955-970, DOI: https://doi.org/10.1016/ j.molmed.2021.07.003.
Sun, Y, Wang, X, Liu, T, Zhu, X & Pan, X 2022, The multifaceted role of the SASP in atherosclerosis: From mechanisms to therapeutic opportunities. Cell & Bioscience, 12: 74.
Suttie, AE (Ed.) 2018, Boorman’s pathology of the rat: Reference and Atlas, 2nd ed, Academic Press, an
Takeda, A, Salmi, M & Jalkanen, S 2023, Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system. Trends in Immunology, 4: 72-86, DOI:10.1016/j.it.2022.10.010.
Tanasiychuk, IS 2004, Cytomorphological characteristics of the cellular composition of the lymph nodes are normal. Journal of Cytology and Genetics, 38: 60-66.
Thangaswamy, S, Bridenbaugh, EA & Gashev, AA 2012, Evidence of increased oxidative stress in aged mesenteric lymphatic vessels. Lymphatic Research and Biology, 10: 53–62, DOI: https://doi.org/ 10.1089/lrb.2011.0022.
Thompson, HL, Smithey, MJ, Surh, CD & Nikolich-Žugich, J 2017, Functional and homeostatic impact of age-related changes in lymph node stroma. Frontiers in Immunology, 8: 706, DOI:  https://doi.org/10.3389/fimmu.2017.00706.
Thompson, HL, Smithey, MJ, Uhrlaub, JL, Jeftiґc, I, Jergoviґc, M, White, SE, Currier, N, Lang, AM, Okoye, A, Park, B, Picker, LJ, Surh, CD & Nikolich-Zugich, J 2019, Lymph nodes as barriers to T-cell rejuvenation in aging mice and nonhuman primates. Aging Cell, 18:e12865, DOI: https://doi.org/10.1111/acel.12865.
Tsyplenkova, VG 2012, Mechanisms of aging and death of cardiomyocytes in non-coronary heart diseases. Archive of Pathology, 74: 22-25.
Turner, VM & Mabbott, NA 2017, Influence of ageing on the microarchitecture of the spleen and lymph nodes. Biogerontology, 18: 723–738, DOI: https://doi.org/10.1007/s10522-017-9707-7.
Vanhoutte, PM 1978, Adrenergic neuroeffector interaction in the blood vessel wall. Federation Proceedings, 37: 181-186.
von der Weid, PY & Zawieja, DC 2004, Lymphatic smooth muscle: The motor unit of lymph drainage. The International Journal of Biochemistry & Cell Biology, 36: 1147-1153, DOI: 10.1016/j.biocel. 2003.12.008.
Wang, S, Huo, T, Lu, M, Zhao, Y, Zhang, J, He, W & Chen, H 2025, recent advances in aging and immunosenescence: Mechanisms and therapeutic strategies. Cells, 14(7): 499, DOI:10.3390/ cells14070499
Wang, X, Vrtiska, TJ, Avula, RT et al. 2014, Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney. Kidney International, 85:677-685, DOI: 10.1038/ki.2013.359.
Xu, X, Wang, B, Ren Ch, Hu, J, Greenberg, DA, Chen, T, Xie, L & Jin, K 2017, Age-related impairment of vascular structure and functions. Aging and Disease. 8(5): 590-610, DOI:10.14336/AD.2017.0430Zhang, K, Farrell, D, Jeyakumar, D, O'Brien, S, Zhao, X & Rezk, SA 2019, Prolymphocytic transformation of lymphoplasmacytic lymphoma: An extremely unusual event. Human Pathology, 90: 106-110, DOI: 10.1016/j.humpath.2018.09.021.
Zhang, L, Pitcher, LE, Yousefzadeh, MJ, Niedernhofer, LJ, Robbins, PD & Zhu, Y 2022, Cellular senescence: A key therapeutic target in aging and diseases. Journal of Clinical Investigation, 132: e158450.
Caspian Journal of Environmental Sciences
Volume 23, Issue 4
October 2025
Pages 979-990

Files

Share

How to cite

Statistics