Immune memory trains aging blood stem cells to inflame
Aging blood stem cells drive chronic inflammation. But what pushes those stem cells into that state in the first place? A corrected version of an influential study sharpens the answer.
Blood cells are continually produced by stem cells in the bone marrow. As those stem cells age, their behaviour changes. They start producing more immune cells that sustain a chronic low-grade inflammation, a process researchers call inflammaging. That inflammation is associated with higher risk of cardiovascular disease, dementia, and other age-related conditions.
The researchers show in a corrected version of their earlier paper in Nature Aging that the aging of blood stem cells is partly driven by a mechanism called trained immunity. This is a form of immune memory in which immune cells are reprogrammed by past infections or other stimuli to respond more rapidly and strongly to new signals. Normally this is beneficial, but in aging the reprogramming can become permanent and contribute to chronic inflammation.
What makes this mechanism distinctive
Trained immunity does not operate through DNA mutations. Instead it works through changes in how genes are switched on or off, without altering the DNA sequence itself. These changes in gene activity (epigenetic changes) can be stable over time and are passed on to new blood cells. The mechanism thus links two well-known aging processes: the transformation of blood stem cells and the accumulation of chronic inflammation.
The correction clarifies details in the data analysis but leaves the main conclusions intact: trained immunity plays a causal role in blood stem cell aging and associated inflammation, at least in the mouse model used. Whether this translates directly to humans is the next research question.
Opportunities for intervention
If trained immunity is a driving factor in inflammaging, that opens new therapeutic avenues. Existing compounds that influence epigenetic changes are already being studied in other contexts. Whether such an approach can also slow the aging of blood stem cells remains an open question, but one that the field is actively pursuing.
Want to research this yourself? Try these search terms in Google Scholar or PubMed:
- trained immunity hematopoietic stem cell aging
- inflammaging epigenetic reprogramming
- blood stem cells chronic inflammation aging