Theorizing that Immunosenescence Contributes to Stem Cell Activity Decline in Aging
Immunosenescence is the term given to the aging of the immune system. In old age the immune system falls into a state of chronic inflammation coupled with a lack of effectiveness: it is overactive to the point of damaging tissues, but lacks the capacity to achieve the goals of destroying pathogens and potentially dangerous cells. Researchers here theorize that the progressive deterioration of the immune system is one contributing factor to the characteristic decline in stem cell activity that also accompanies aging, at least where it involves mesenchymal stem cells (MSCs). They propose that this effect is mediated through the interaction of hematopoietic stem cells, responsible for generating immune cells, and mesenchymal stem cells in the bone marrow where they both reside:
Several lines of evidence indicate that the decline in stem cell function during ageing can involve both cell intrinsic and extrinsic mechanisms. The bone and blood formation are intertwined in bone marrow, therefore, haematopoietic cells and bone cells could be extrinsic factors for each other in bone marrow environment. There is growing evidence in animal studies and invertebrate models that the stem cell niche, one of the extrinsic mechanisms, is important for the regulation of cellular ageing in stem cells. We uncovered that there are age-related intrinsic changes in human mesenchymal stem cells. In this study, we assess the paracrine interactions of human bone marrow haematopoietic cells on mesenchymal stem cells.Our data demonstrate that there are paracrine interactions of haematopoietic cells, via soluble factors, such as TNF-α, PDGF-β or Wnts, etc., on human mesenchymal stem cells; the age-related increase of TNF-α in haematopoietic cells suggests that immunosenescence, via the interactions of haematopoietic cells on mesenchymal stem cells, may be one of the extrinsic mechanisms of skeletal stem cell function decline during human skeletal ageing. TNF-α has a central role in bone pathophysiology and its action in the skeleton results in increased bone resorption by stimulation of osteoclastogenesis and impaired bone formation by suppressing recruitment of osteoblasts from progenitor cells, inhibiting the expression of matrix protein genes, and stimulating expression of genes that amplify osteoclastogenesis.
Our data implied that besides the current approaches to intervene in osteoporosis, such as targeting on osteoclasts to stop bone resorption or osteoblasts to increase bone formation, there may be a new approach that targets the interactions of haematopoietic cells on osteoblast precursors to identify potential intervention for osteoporosis and bone fracture, and to develop therapeutic strategies to prevent or restore skeletal tissue degeneration and loss in the ageing population.