Review Volume 13, Issue 15 pp 19920—19941

Cellular senescence in lymphoid organs and immunosenescence

Aged bone marrow microenvironment with accumulated SnCs is not conducive for its normal functionality. SASP and ROS mediate dysfunction and DNA damage in HSCs, respectively and lead to a change in the HSC repertoire and exhaustion of the functional HSC reservoir. RANKL mediates the accumulation of adipocytes that produce ADFs. CCL5 and ADFs mediate the establishment of myeloid skewing in HSCs. SASP mediated inflammation can dysregulate the adequate production of homing signals and survival factors by the MSCs which can lead to the depletion of selective immune cell types. The increased ROS and SASP mediated inflammation causes damage to the surrounding cells and induces senescence by means of the bystander effect. SnCs such as osteocytes can produce SASP that is detrimental to the bone housing which encloses them. In the absence of rapid clearance of SnCs, this becomes a self-perpetuating cycle of dysfunction and damage causing severe immunosenescence. Abbreviations: SnC: Senescent cell; SASP: Senescence associated secretory phenotype; ROS: Reactive Oxygen Species; HSC: Hematopoietic stem cell; CLP: Common lymphoid progenitor; CMP: Common myeloid progenitor; MSC: Mesenchymal stem cell; MCSF: Mesenchymal stem cell derived factors; ADF: Adipocyte derived factors; CCL5: Chemokine Ligand 5; RANKL: Receptor activator of nuclear factor kappa-Β ligand.

Figure 2. Aged bone marrow microenvironment with accumulated SnCs is not conducive for its normal functionality. SASP and ROS mediate dysfunction and DNA damage in HSCs, respectively and lead to a change in the HSC repertoire and exhaustion of the functional HSC reservoir. RANKL mediates the accumulation of adipocytes that produce ADFs. CCL5 and ADFs mediate the establishment of myeloid skewing in HSCs. SASP mediated inflammation can dysregulate the adequate production of homing signals and survival factors by the MSCs which can lead to the depletion of selective immune cell types. The increased ROS and SASP mediated inflammation causes damage to the surrounding cells and induces senescence by means of the bystander effect. SnCs such as osteocytes can produce SASP that is detrimental to the bone housing which encloses them. In the absence of rapid clearance of SnCs, this becomes a self-perpetuating cycle of dysfunction and damage causing severe immunosenescence. Abbreviations: SnC: Senescent cell; SASP: Senescence associated secretory phenotype; ROS: Reactive Oxygen Species; HSC: Hematopoietic stem cell; CLP: Common lymphoid progenitor; CMP: Common myeloid progenitor; MSC: Mesenchymal stem cell; MCSF: Mesenchymal stem cell derived factors; ADF: Adipocyte derived factors; CCL5: Chemokine Ligand 5; RANKL: Receptor activator of nuclear factor kappa-Β ligand.