The Inflammatory Burden of Infection Accelerates Hematopoietic Aging

Researchers here provide evidence for the inflammatory burden of infection to accelerate the aging of the hematopoietic system responsible for generating blood and immune cells. A greater exposure to infectious disease throughout life may be causing presently irreversible damage in the stem cell populations that produce the immune system. It is already known that restoration of these stem cell populations is an important target for the rejuvenation of the aged immune system, along with regeneration of the thymus and clearance of misconfigured and damaged populations of immune cells. It is unclear as to which of the many potential approaches to rejuvenation of hematopoietic stem cells will first succeed to a useful degree, but it seems likely that some form of cell therapy will be needed, an outright replacement of worn, damaged, and missing cells with a new and competent population.

Blood stem cells in the bone marrow provide a lifelong replenishment of the different cell types making up the blood system. In addition, they are also of capable of making new stem cells, in a process called "self-renewal". In older people, diseases of the hematopoietic system often occur, such as anemia or certain forms of blood cancer. Such diseases are thought to be caused by an age-associated decline in stem cell self-renewal. However, mouse models housed under highly controlled, pathogen-free conditions, rarely spontaneously develop such age-related diseases.

According to experts, the cause of this age-related loss of function of the hematopoietic system is a chronic low-grade inflammatory condition called inflammaging, that only develops in later life and impairs the function blood stem cells. "However, the question that we wanted to answer was whether inflammation and infections in early life can permanently damage blood stem cells and thus promote aging of the blood system. We have therefore carried out time-consuming experiments to determine for how we observe an inhibitory effect on stem cell function following infection and inflammation, and came to the surprising conclusion that we never see any evidence of stem cell recovery, suggesting that this process is long-lasting or perhaps even irreversible."

The researchers subsequently identified the cause of the dysfunctional hematopoiesis: Blood stem cells failed to self-renew as they were forced to divide in response to the inflammatory stimuli. The long-term consequence of a lack of self-renewal is that the hematopoietic system becomes exhausted. "This observation in mice contradicts common doctrine: we had previously believed that, after inflammatory challenge, blood stem cells revert into a so-called dormant state that preserves their capacity for self-renewal."



I just watched an interesting talk given by Shiri Gur-Cohen who does stem cell research. They did an experiment where they put stem cells from young mice into old mice and from old into young.

The interesting finding was that the the old cells into young mice were rejuvenated and the young cells into old had poor function, just like old cells in old animals.

So the old environment is the problem and to me this explains why stem cell therapy has mixed or poor results in general.

Posted by: Lee at August 11th, 2022 8:52 AM

Is it considered heretic to raise the question what kind of damage vaccinations repeated in short intervals do to the hematopoietic stem cell population?

Posted by: Jones at August 11th, 2022 12:54 PM

@Jones: I would balance any potential vaccination damage with the more severe inflammation induced by the *actual* infection. Getting infected induces much more inflammaging than the vaccine.

Posted by: Edward F Greenberg at August 13th, 2022 9:00 AM

@EF Greenberg
That would be true if the vaccine actually prevented infection.

Posted by: Jones at August 14th, 2022 12:34 PM
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