Aging in the bone marrow: when hematopoiesis gets clonal

PURPOSE OF REVIEW: It has been known that the cytokine TNF (tumor necrosis factor alpha) influences hematopoiesis for decades. We now know that increases in TNF in the aging microenvironment favor the persistence and expansion of myeloid progenitors, especially those that contain mutations associated with clonal hematopoiesis of indeterminate potential (CHIP). Herein, we will examine both seminal and recent studies that have advanced our understanding of how TNF shapes hematopoietic development during aging and influences clonal dynamics in CHIP. RECENT FINDINGS: Elevated levels of TNF contribute to engraftment and expansion of CHIP-mutant clones; however, there are subtle differences between the specific CHIP mutations. Sex differences in levels of TNF may contribute to differences in the frequency and types of CHIP mutations found in males and females. Anti-TNF inhibitors reduce the frequency of CHIP mutation containing clones in multiple inflammatory diseases. SUMMARY: The elevated levels of TNF that occur with both age and chronic inflammatory conditions contribute to both myeloid skewing and CHIP. Anti-TNF drugs reduce problematic changes in myeloid hematopoiesis. Anti-TNF drugs are not an effective strategy to treat CHIP and more research is needed as to whether other anti-inflammatory strategies, including diet and exercise, are also effective.