Transitional senescent monocytes drive age-related inflammation in humans
Researchers identified a transient senescent-like monocyte state governed by the transcription factor AP-1 that primes cells toward inflammatory and sepsis-associated states.
bioRxiv : the preprint server for biology · Vasilopoulos T et al. · Paper published 13 Sep 2026
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.
Why it matters
Identifying how transitional senescent states foster age-related inflammation reveals key regulatory mechanisms behind immune aging. It also points to AP-1 as a specific target for modulating systemic inflammation in older adults.
Caveats
This work is a preprint that has not yet undergone peer review. The conclusions are derived from observational profiling and transcriptomic dataset integration without reported interventional testing.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
A transitional senescence program drives inflammatory monocyte state expansion in aging humans
Vasilopoulos T, Turano PS, Garza-Martínez L et al.
bioRxiv : the preprint server for biology · 13 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Humans
- Status
- Preprint
More on Inflammaging
See allCranial bone marrow monocytes drive brain injury inflammation and respond to fenofibrate
Targeting PPARα deficiency in cranial bone marrow monocytes improved cognitive function and reduced neurodegeneration markers in older patients with chronic brain injury.
Science translational medicine · Lu Z et al.
Somatic blood mutations associate with accelerated frailty and functional decline in humans
In a preprint analyzing over 730,000 adults, researchers linked clonal hematopoiesis to faster physical decline mediated by T-cell changes.
medRxiv · Zhao K et al.
Impaired glymphatic clearance links inflammation to accelerated brain aging in schizophrenia
Neuroimaging and post-mortem transcriptomics connect disrupted astrocytic aquaporin-4 polarization and blood-brain barrier breakdown to increased epigenetic and brain age.
bioRxiv · Tan X et al.
ASXL1 mutations in clonal hematopoiesis accelerate aortic valve calcification
Large human cohort data and cell experiments show that ASXL1-driven clonal hematopoiesis worsens aortic valve hemodynamics and promotes calcification through inflammatory signaling.
medRxiv · Small A et al.
Loss of SATB1 alters 3D genome architecture in aged mouse T cells
Declining levels of the chromatin organizer SATB1 disrupt genomic boundaries and drive inflammatory gene activation in naive CD4+ T cells.
Science advances · Wang B et al.