Myeloid Heterogeneity in Inflammaging

Aging is not simply a passive decline — it is an active biological process driven in part by a persistent, low grade sterile inflammation that permeates tissues, erodes resilience, and fuels the onset of chronic disease. This state, known as inflammaging, sits at the intersection of immunology and geroscience and is now recognised as one of the most consequential drivers of conditions including neurodegeneration, cardiovascular disease, metabolic dysfunction, osteoarthritis, and frailty. Yet despite decades of research, the cellular machinery that sustains inflammaging remains incompletely mapped.Myeloid cells are central to this story. Monocytes, macrophages, neutrophils, dendritic cells, mast cells, and their bone marrow progenitors collectively form the frontline of innate immunity and are among the most plastic cells in the body. Their identity and function are continuously shaped by tissue context, metabolic state, epigenetic memory, and inflammatory history. In aging, each of these layers is disrupted. Myeloid biased output from the bone marrow, clonal expansion of somatically mutated progenitors, accumulation of dysfunctional tissue resident macrophages, and a progressive blunting of stimulus responsiveness all conspire to generate a myeloid compartment that is simultaneously overactivated and functionally impaired.What has become clear from the latest wave of single cell and spatial technologies is that myeloid populations in aged tissues are not a monolith. They are a richly heterogeneous collection of states — some proinflammatory, some immunosuppressive, some locked in senescence associated secretory programs, and others representing entirely novel aging specific phenotypes with no clear counterpart in youth. Cataloguing, contextualising, and ultimately targeting this diversity represents one of the most exciting frontiers in aging biology.This Research Topic brings together mechanistic, translational, and clinical perspectives to build a comprehensive and timely picture of myeloid heterogeneity across the aging process. We welcome original research, systematic reviews, meta analyses, and expert perspectives addressing themes including:1. Single cell and spatial transcriptomic profiling of myeloid populations in aged tissues2. Monocyte subset dynamics and functional reprogramming with age3. Macrophage identity, tissue residency, and homeostatic failure in aging organs4. Myeloid progenitor skewing and clonal haematopoiesis of indeterminate potential5. Epigenetic and metabolic remodelling of myeloid cells across the life course6. Crosstalk between senescent cells and myeloid populations7. Neutrophil heterogeneity, aging associated dysfunction, and resolution defects8. Dendritic cell subsets and the deterioration of innate immune sensing9. Sex as a biological variable in myeloid aging10. Tissue specific myeloid contributions to neuroinflammation, atherosclerosis, sarcopenia, and metabolic disease11. Therapeutic strategies targeting myeloid dysfunction to resolve or reverse inflammagingThe myeloid system is both a mirror of biological age and an active architect of the aging process. By defining its heterogeneity with the precision that modern tools now allow, this Research Topic aims to shift the field from broad descriptions of immune aging toward a mechanistic, cell resolved understanding that can translate into real therapeutic opportunity. We invite researchers across immunology, geroscience, computational biology, and clinical medicine to contribute to what we anticipate will be a landmark collection at the forefront of aging research. Topic editors: Ravi K Komaravolu Ph.D., Catherine Hedrick Source: https://www.frontiersin.org/research-topics/81774/myeloid-heterogeneity-in-inflammaging