Abstract
One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of mesenchymal cells with other cells having the same embryological origin. Newly formed adipocytes were also observed in the trabecular matrix of elderly people’s bones, associated with myeloid cells. In this study, we have investigated the relationship between immature myeloid-derived suppressor cells (I-MDSCs) and mesenchymal stem cells (MSCs) in bone marrow (BM) samples harvested from 57 patients subjected to different orthopedic surgeries. Patients aged from 18 to 92 years were considered in order to compare the cellular composition of bone marrow of young and elderly people, considered a biomarker of immunity, inflammation, and bone preservation. The I-MDSC percentage was stable during aging, but in elderly people, it was possible to observe a strong basal immunosuppression of autologous and heterologous T cells’ proliferation. We hypothesized that this pattern observed in elders depends on the progressive accumulation in the BM of activating stimuli, including cell–cell contact, or the production of different cytokines and proteins that induce the differentiation of bone marrow mesenchymal stem cells in adipocytes. The collected data provided underline the importance of specific biomarkers of aging that promote a reduction in immune response and incremented inflammatory pathways, leading to bone reabsorption in elderly people.
Highlights
A common hallmark of the aging of primary lymphoid organs in humans is the progressive accumulation of adipose tissue [1]
The number of red blood cells (RBCs) and the percentage of neutrophils, a marker of traumatic inflammation, were similar in all groups, ruling out the likelihood that the increase in cytokines observed during aging depended on the different sites of bone marrow (BM) sampling or the traumas (Table S1)
Our data show that the cross-talk between myeloid and mesenchymal stem cells of human bone marrow induces suppression in immature myeloidderived suppressor cells (I-Myeloid-derived suppressor cells (MDSCs)) and adipogenesis in BM-Derived MSC (BM-MSC)
Summary
A common hallmark of the aging of primary lymphoid organs in humans is the progressive accumulation of adipose tissue [1]. A correlation between adipose accumulation in the bone marrow and decreases in bone mass has been reported in pathological conditions associated with bone loss, such as aging [7,8,9]. As both osteoblasts and adipocytes originate from MSCs [10], a large number of extracellular and intracellular signals and transcription factors balance adipogenesis and osteoblastogenesis [11,12]. The inhibition of p38MAPK activity in 3T3-L1 fibroblasts blocks their differentiation in adipocytes by decreasing the phosphorylation of C/EBPβ and of PPAR-γ [16], required for terminal adipogenesis, as well as the expression of specific adipocyte genes such as adiponectin, GLUT4, and leptin. A recent study demonstrated a correlation between the expression of IL-6R and MB-MSCs’ adipogenesis differentiation, accompanied by the same trend of p38 phosphorylation, suggesting that the IL-6/IL-6R pathway plays a significant role in tissue regeneration and cell differentiation [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
