Recently, in a research report entitled "Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging" published in Cell Stem Cell, scientists from the German Cancer Research Center and other institutions studied, scientists from the German Cancer Research Center and other institutions have found that in the mouse body, inflammation in the early and middle stages may lead to a permanent decline in the function of functional hematopoietic stem cells. When the body is challenged with inflammation, the ability of hematopoietic stem cells to regenerate is inhibited for at least a year.
This may suggest that infection and inflammation may act as prominent drivers of age-related functional decline in tissues, and that mice exposed to challenges such as those described above develop clinically relevant aging signatures that are often observed in elderly organisms.
A lifelong supply of the various cell types that make up the body's blood system is provided by hematopoietic stem cells in the bone marrow. In addition, they have the capacity to generate new stem cells, a process known as "self-renewal," which happens in older adults. Hematopoietic system disorders, like anemia or a specific type of blood cancer, are frequently seen in mouse models of age-related diseases, which rarely happen spontaneously.
According to the researchers, age-related loss of hematopoietic system function is caused by a chronic low-grade inflammatory condition called inflammatory aging, which occurs only in later life and impairs the function of the body's hematopoietic stem cells.
"However, the question we wanted to answer," said researcher Mick Milsom, "was whether inflammation and infection in early life could permanently impair the function of hematopoietic stem cells, thereby promoting the aging of the body's blood system." To this end, the scientists carried out laborious experiments to ascertain how they saw the inhibitory effects of stem cell function in the body after infection and inflammation, and they also came to the unexpected conclusion that there was no evidence of stem cell recovery, indicating that the process might be lengthy and even irreversible.
The researchers noted that mice were repeatedly exposed to pro-inflammatory agents or bacteria, with injections spaced by 4 weeks and no stem cell recovery in between challenges. This indicates that these therapies ultimately result in more inhibiting effects. This may support a theory explaining how age-related tissue dysfunction and disease development arises, according to which even isolated episodes of infection or inflammation can inhibit stem cell function over the course of months or years.
The researchers then identified the cause of abnormal hematopoietic function in the body. When hematopoietic stem cells are driven to divide in response to inflammatory stimuli, they often fail to self-renew, and the long-term consequence of lack of self-renewal is the depletion of the hematopoietic system.
"The observations in mice may contradict common theory," the researchers said. Previously, they believed that after experiencing an inflammatory challenge, hematopoietic stem cells would return to a so-called dormant state, thereby maintaining their ability to self-renew. This study may have made an unexpected discovery.
