A well-balanced immune system is the key to health, and the years flown away from your calendar have been breaking this crucial balance within your body’s defense system, slowly but constantly. So, it is not only wrinkles on your face you get but also a ramshackle immune system when the age finally catches up with you, leaving you vulnerable to infections such as COVID-19.
All cells and tissues in the human body are genetically programmed to age and our body’s beloved defense cells, immune cells, are not exempt from that. Scientists refer to this phenomenon as “immunosenescence”, a fancy name for immune aging. Aging of the immune system will likely be a major public health problem in the not too distant future as it is projected that the geriatric population1* will exceed 2.1 billion, making up more than 20% of the world population by 2050. [1] In fact, immune aging has already been gathering much attention nowadays thanks to the recent pandemic and it’s one of the latest victims, President Donald Trump, who is 74. Because the risk for the severe form of COVID-19 significantly goes up with the patient’s age, and recent studies show that 95% of fatalities from COVID-19 occur in patients aged 65 or above, medical specialists at the Walter Reed Medical Center, where the President has been treated, did not hesitate to try an experimental anti-viral drug, Remdesivir, on him.[2]
Immune aging can not solely be held responsible for the increased age-associated mortality as it is not uncommon that geriatric patients have underlying non-communicable diseases such as metabolic disorders, heart diseases, cancers. [3] However, the declined defensive capacity of the immune system still plays a great role in age-related vulnerability to infections as well as in reduced responses to vaccines. Therefore, researchers from the immunology field have been extensively investigating molecular mechanisms leading to immunosenescence and ways to combat it. Undoubtedly, reduced productivity of bone marrow that leads to the generation of fewer white blood cells is one of the well-established hallmarks of the immune aging process. [4]
Not just the quantity but also the quality of immune cells is being largely affected by aging. One recent study indeed proved that the immune system of old individuals has defects in forming micro-factories, germinal centers, where B lymphocytes2* differentiate into specialised antibody-secreting cells. [5] This also pertains to why some elderly people can not exhibit robust immune responses when they get a flu jab. Another relevant piece of data came from a study conducted by the Oxford Vaccine group on mice and showed that the Oxford Vaccine, ChAdOx1 nCoV-19, induced lower levels of germinal center B lymphocytes in aged mice compared to in younger counterparts. [6] What vaccine trials in humans will show us, of course, we don’t know yet, but another clinical implication of immune aging in the recent pandemic may be that people who are older than 65 will require a booster dose in order for the COVID vaccine to work efficiently.
Moreover, the immune plasma taken from individuals who recovered from COVID contains neutralising antibodies that can attack and kill the virus. The declined antibody responses to coronavirus in some patients constitute the rationale behind the plasma therapy which has lately been approved by the Food and Drug Administration (FDA). [7] This mode of treatment can be, therefore, extremely beneficial to the aged population that suffers from poor immune functions due to age or other reasons.
It is good to touch on another fancy term “inflamm-aging” at this point. As the term suggests, it describes the inflammation driven by age. We know from the literature that immune cells from the elderly are prone to secrete pro-inflammatory chemicals called cytokines, which establishes the molecular and cellular basis of inflamm-aging, and yet, the geriatric age group is predisposed to microbial intruders. [8] It might sound like a paradox at first glance, but aberrant pro-inflammatory responses do not confer physiological protection from infectious agents. In contrast, they do more harm than good. Indeed, a prolonged and amplified unaimed inflammatory state in old individuals may lead to a quite dangerous medical condition called “cytokine storm”. It is basically the kamikaze attempt of the immune system in which it overreacts to the pathogen and damages our own body’s organ systems. It is one of the serious complications witnessed also in a fraction of elderly COVID patients such that in the case of a cytokine storm, anti-inflammatory treatments that block certain cytokines responsible for overt immune responses are required. [9] You did not hear that wrong, doctors do suppress immune responses in COVID patients when the immune system starts to fight the bug at the cost of our own life. In a nutshell, I end the paragraph here with my own made up fancy term “immunebalance” summarising all the points made above.
In conclusion, immunosenescence is a field that studies age-related changes in our immune system. As the average age of the world population increases and the elderly people being vulnerable to various infections such as COVID, we will inevitably be hearing about immunosenescence more and more. Therefore, new treatment modalities are urgently needed to slow down the immune aging process and compensate for the defective defense capacity in the elderly population.
1* old, elderly
2* cell type responsible for antibody-related immune responses
Author: Yavuz F. Yazicioglu, MD
DPhil student in Molecular and Cellular Medicine, St. Hugh’s College
Email: yavuz.yazicioglu@st-hughs.ox.ac.uk
References
[1] UN, World Population Prospects 2019
[2] J. P. A. Ioannidis, C. Axfors, and D. G. Contopoulos-ioannidis, “Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters,” Environ. Res., vol. 188, p. 109890, 2020.
[3] J. B. Gong, X. W. Yu, X. R. Yi, C. H. Wang, and X. P. Tuo, “Epidemiology of chronic noncommunicable diseases and evaluation of life quality in elderly,” no. February, pp. 64–66, 2018.
[4] T. Pritz, B. Weinberger, and B. Grubeck-loebenstein, “The aging bone marrow and its impact on immune responses in old age,” Immunol. Lett., vol. 162, no. 1, pp. 310–315, 2014.
[5] K. Shankwitz, S. Pallikkuth, T. Sirupangi, D. Kirk, K. Kyle, B. Russel, R. Pahwa, L. Gama, R. A. Koup, L. Pan, F. Villinger, S. Pahwa, C. Petrovas, and M. G. Foundation, “Compromised steady-state germinal center activity with age in nonhuman primates,” no. November 2019, pp. 1–14, 2020.
[6] N. Van Doremalen, T. Lambe, A. Spencer, S. Belij-rammerstorfer, J. N. Purushotham, J. R. Port, V. Avanzato, T. Bushmaker, M. Ulaszewska, F. Feldmann, E. R. Allen, H. Sharpe, J. Schulz, M. Holbrook, A. Okumura, K. Meade-white, C. Bissett, C. Gilbride, B. N. Williamson, R. Rosenke, D. Long, A. Ishwarbhai, R. Kailath, L. Rose, S. Morris, C. Powers, J. Lovaglio, P. W. Hanley, D. Scott, G. Saturday, E. De Wit, C. Sarah, and V. J. Munster, “ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques 2 3,” 2020.
[7] M. J. Joyner, J. W. Senefeld, S. A. Klassen, J. R. Mills, P. W. Johnson, E. S. Theel, C. C. Wiggins, K. A. Bruno, A. M. Klompas, R. Elizabeth, K. L. Kunze, M. A. Sexton, J. C. D. Soto, S. E. Baker, J. R. A. Shepherd, N. Van Helmond, S. Paneth, D. Fairweather, R. S. Wright, R. E. Carter, A. Casadevall, C. M. Van Buskirk, L. Jeffrey, J. R. Stubbs, R. F. Rea, D. O. Hodge, E. R. Whelan, A. J. Clayburn, K. F. Larson, J. G. Ripoll, K. J. Andersen, M. R. Buras, N. P. Matthew, J. J. Dennis, R. J. Regimbal, P. R. Bauer, and J. E. Blair, “Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19 : Initial Three-,” pp. 1–31, 2020.
[8] C. Franceschi, P. Garagnani, P. Parini, C. Giuliani, and A. Santoro, “Inflammaging: a new immune–metabolic viewpoint for age-related diseases,” Nat. Rev. Endocrinol., vol. 14, no. October, 2018.
[9] D. Ragab, H. S. Eldin, M. Taeimah, and R. Khattab, “The COVID-19 Cytokine Storm ; What We Know So Far,” vol. 11, no. June, pp. 1–4, 2020.
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