Recently, in a research report published in the international journal Cell Stem Cell entitled "infant exposure drives long-lived impact of hematopoietic stem cell self-renewal activity and accelerated aging", scientists from German Cancer Research Center and other institutions found through research that in the mouse body, inflammation in the early and middle stages may lead to permanent decline in the function of functional hematopoietic stem cells, When the body is challenged by inflammation, the ability of hematopoietic stem cells to regenerate will be suppressed for at least one year, which may indicate that infection and inflammation may play the role of a prominent driver of age-related functional decline in the tissue. Mice exposed to such challenges in early years will show clinically relevant aging characteristics, which are often observed in the elderly body.
The hematopoietic stem cells in the bone marrow can provide lifelong supply for different cell types constituting the body's blood system. In addition, they can also produce new stem cells. This process is called "self-renewal". In the elderly, diseases of the hematopoietic system usually occur, such as anemia or some form of blood cancer. Such diseases are considered to be caused by the decline of self-renewal ability of age-related stem cells, However, age-related diseases rarely occur spontaneously in mouse models reared under highly controlled, pathogen free conditions.
According to the researchers, the reason for age-related loss of hematopoietic system function is the chronic low-level inflammatory condition called inflammatory aging, which only occurs in later years and will damage the function of hematopoietic stem cells of the patient. Researcher Mick Milsom said, however, the question we want to answer is whether inflammation and infection in early years will permanently damage the function of hematopoietic stem cells, thus promoting the aging of the body's blood system. To this end, researchers conducted time-consuming experiments to determine how they observed the inhibitory effect of stem cell function after infection and inflammation. At the same time, they came to a surprising conclusion that they did not observe any evidence of stem cell recovery, which indicates that this process may be a long-term or even irreversible process.
Image source: cell stem cell (2022) DOI:10.1016/j.stem.2022.06.012
The researchers said that mice would be challenged by proinflammatory substances or bacteria for many times. The interval between two injections was 4 weeks, and there was no recovery of stem cells between each challenge. This means that these treatments will eventually lead to additional inhibitory effects, which may support a model that can explain age-related tissue dysfunction and disease occurrence, That is, independent infection or inflammation may have a cumulative inhibitory effect on the function of stem cells, even if it is several months or years apart.
Subsequently, researchers identified the cause of abnormal hematopoietic function in the body. When hematopoietic stem cells are driven to split to respond to inflammatory stimuli, they often fail to carry out self-renewal, and the long-term consequence of lack of self-renewal is the exhaustion of the hematopoietic system. The researchers said that this observation in the mouse body may contradict the general theory. Previously, they thought that after experiencing the challenge of inflammation, Hematopoietic stem cells will return to the so-called dormant state, so as to maintain their self-renewal ability. This study may have unexpected findings.
Researcher Milsom said that it is important that the inflammation of young mice will lead to persistent changes in the hematopoietic system, which is similar to the age-related changes that often occur in the elderly, including anemia and reduction of the number of cells in the bone marrow; Inflammation and infection in the young age of the body seem to accelerate the aging of its hematopoietic system. In the next step, researchers will continue to conduct in-depth research to explore whether preventive anti-inflammatory therapy can slow down age-related hematopoietic system diseases while still maintaining the immune response of the body to resist the invasion of pathogens.
Original source:
Ruzhica Bogeska，Ana-Matea Mikecin，Paul Kaschutnig，et al. Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging, Cell Stem Cell (2022). DOI: 10.1016/j.stem.2022.06.012
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