Transitional senescent monocytes drive age-related inflammation in humans

In aging humans, dysfunctional monocyte states contribute to systemic inflammation, but the underlying regulatory networks have remained unclear. In a new preprint, researchers used bulk and single-cell multidimensional integrative profiling to track monocyte state transitions during human aging. They found that a transient senescent-like population arising from classical CD14++CD16- monocytes drives the accumulation of an inflammatory monocyte state. This transition is orchestrated by the transcription factor AP-1, which acts on a pre-established chromatin landscape to rewire the cellular gene regulatory network. This process activates both senescence- and age-associated inflammatory transcriptional programs. Additionally, integrating these findings with clinical transcriptomic datasets revealed that aged and senescent-like monocytes are transcriptionally primed toward sepsis-associated states.