The impact of oxidative stress, inflammation, and senescence on the maintenance of immunological memory in the bone marrow in old age

Abstract

The bone marrow (BM) provides a preferential survival environment for the long-term maintenance of antigen-experienced adaptive immune cells. After the contact with antigens, effector/memory T cells and plasma cell precursors migrate to the BM, in which they can survive within survival niches in an antigen-independent manner. Despite this, the phenotype of adaptive immune cells changes with aging, and BM niches themselves are affected, leading to impaired long-term maintenance of immunological memory in the elderly as a result. Oxidative stress, age-related inflammation (inflammaging), and cellular senescence appear to play a major role in this process. This review will summarize the age-related changes in T and B cell phenotype, and in the BM niches, discussing the possibility that the accumulation of highly differentiated, senescent-like T cells in the BM during aging may cause inflammation in the BM and promote oxidative stress and senescence. In addition, senescent-like T cells may compete for space with other immune cells within the marrow, partially excluding effector/memory T cells and long-lived plasma cells from the niches.

Keywords: ROS; aging; bone marrow; immunological memory; immunosenescence; inflammation.

Figure 1. Hypothetical structure of a BM niche for CD8⁺ and CD4⁺ effector/memory T cells

Myeloid cells (monocytes and DCs) and stromal cells produce and trans-present IL-15 to effector/memory CD8⁺ and CD4⁺ T cells. IL-7 is produced and secreted mostly by stromal cells.

Figure 2. The impact of ‘inflammaging’, cellular senescence, oxidative stress and CMV on the maintenance of immunological memory in the BM