The aging of the immune system and its implications for transplantation

Abstract

By the last third of life, most mammals, including humans, exhibit a decline in immune cell numbers, immune organ structure, and immune defense of the organism, commonly known as immunosenescence. This decline leads to clinical manifestations of increased susceptibility to infections, particularly those caused by emerging and reemerging microorganisms, which can reach staggering levels—infection with SARS-CoV-2 has been 270-fold more lethal to older adults over 80 years of age, compared to their 18–39-year-old counterparts. However, while this would be expected to be beneficial to situations where hyporeactivity of the immune system may be desirable, this is not always the case. Here, we discuss the cellular and molecular underpinnings of immunosenescence as they pertain to outcomes of solid organ and hematopoietic transplantation.

Contribution of circulating monocytes in maintaining homeostasis of resident macrophages in postnatal and young adult mouse cochlea

“…However, during the adult stages, there was an increased rate of monocytes recruited from the systemic circulation; moreover, Iba1 + /CD11b − or Iba1 + /Ms4a3 − cochlear macrophages gradually decreased with age. These findings suggested the aging of the immune system as previously shown 20 , Additionally, we studied the immunohistochemistry for both Iba1 and CD11b to assess the distribution of resident macrophages and precursors derived from systemic circulation in the cochlea. Iba1 − /CD11b + cells are considered precursors of tissue-resident macrophages derived from the FL or BM in the adult cochlea 8 , 21 .…”

Immune responsiveness in stable kidney transplantation patients: Complete inhibition of T‐cell proliferation but residual T‐cell activity during maintenance immunosuppressive treatment

“…We also explored additional factors that could potentially influence or reflect the immune status of transplantation patients. The patient's age and chronic immune activation by the allograft are known to affect inhibitory T‐ and B‐cell populations, 9,24,25 making monitoring of these cell subsets an interesting biomarker for immune activity. The number of regulatory T cells, transitional B cells, exhausted T cells, and CD28‐CD8+ T cells has previously been associated with a lower rejection risk after kidney transplantation 26–28 .…”

“…There are countless factors that can affect patients' sensitivity to the immunosuppressive treatment regimen, including age, gender, genetic variability, and drug–drug interactions. 8 , 9 , 10 , 11 , 12 Some of these factors (e.g., CYP‐polymorphisms or drug–drug interactions), directly affect the drug concentration and are usually accounted for by individual TDM. For other factors (e.g., age, lifestyle, and immune variability), it is more difficult to understand and predict how these affect drug efficacy.…”

“…TDM has been shown to be effective but does not necessarily correlate best with the biological activity of the CNIs and MMF. There are countless factors that can affect patients' sensitivity to the immunosuppressive treatment regimen, including age, gender, genetic variability, and drug–drug interactions 8–12 . Some of these factors (e.g., CYP‐polymorphisms or drug–drug interactions), directly affect the drug concentration and are usually accounted for by individual TDM.…”

Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial

“…Moreover, aging is intricately associated with a constellation of factors, including immunosenescence, cognitive decline, reduced social interactions, diminished physical activity, decreased grip strength, sarcopenia, osteopenia, abnormal baroreflex sensitivity, postural instability, an increased risk of falls, slowness, fatigue, poor responses to stress, anorexia, anemia, the presence of chronic diseases, heightened susceptibility to illness, hospitalization, and death ( 6 - 10 ). Various elements such as widowhood, lower income, limited educational attainment, a sedentary lifestyle, and alcoholism contribute to a deteriorating quality of life during normal aging (senescence), resulting in abnormal aging (senility), and frailty with increased healthcare costs ( 11 - 13 ).…”