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New immune cell linked to age‑related inflammation
A newly identified immune cell subtype in visceral (deep abdominal) fat appears to contribute to the low‑grade, chronic inflammation that increases with age, according to preliminary studies in mice published in Nature Aging on 2 September. The research team used imaging and single‑cell RNA analysis to map macrophages — pathogen‑eating white blood cells — in fat tissue and discovered a previously unrecognized population that emerges only in older animals.
Study co‑author Vishwa Deep Dixit, an immunobiologist at Yale University, said: "We did not anticipate that there would be a completely new cell type." Co‑author Elsie Gonzalez‑Hurtado, also at Yale, noted that prior studies lacked a clear characterization of the diverse macrophage populations in fat.
Scientific background: inflammaging and fat‑resident macrophages
What is inflammaging?
Inflammaging refers to the progressive, low‑grade inflammatory state that many organisms develop with age. Normally, inflammation is an acute, protective response to infection or injury. But with ageing, inflammatory signaling can become persistent, contributing to tissue dysfunction and increased risk of chronic conditions such as metabolic disease, cardiovascular disease and neurodegeneration.
Why study visceral fat?
Visceral fat surrounds internal organs and hosts a complex immune microenvironment. Macrophages in fat tissue clear cellular debris and pathogens and also help regulate lipid metabolism and local tissue homeostasis. Changes in the number, location and gene activity of these macrophages can shift tissue function toward either repair or chronic inflammation.
Study approach and key findings
To profile macrophage diversity, the investigators examined visceral fat from young and aged mice. They combined high‑resolution imaging with single‑cell RNA sequencing, which classifies cells by the RNA they express — a readout of which genes are active and what functional programs a cell may be performing.
The analysis revealed 13 distinct visceral‑fat macrophage subtypes. Several of these populations changed in abundance with age. Notably, a novel macrophage subtype that carries transcriptional signatures linked to inflammatory pathways appeared only in older mice. This age‑associated population expressed genes connected to inflammatory signaling and lipid handling, suggesting it could both promote inflammation and influence local lipid balance.
Sex differences also emerged: a nerve‑associated macrophage subtype declined in older female mice but remained stable in males, while a vascular‑associated macrophage population dropped in older males but not females. These sex‑specific trajectories imply that male and female fat immune compartments may age differently, with potential consequences for metabolic and inflammatory disease risks.
Implications, caveats and future directions
The identification of an age‑specific macrophage subtype offers a plausible cellular mechanism for aspects of inflammaging and hints at links between immune cell changes and altered lipid metabolism in ageing tissues. However, the findings are preliminary and limited to a mouse model. Whether the same cell type exists in human visceral fat, and whether it causally drives age‑related inflammation, remain open questions.
If validated in humans, this cell population could become a target for interventions aimed at reducing chronic inflammation and metabolic dysfunction in older adults. Strategies may include drugs that modulate macrophage polarization, immune signaling pathways, or local lipid handling.
Expert Insight
Dr. Aisha Rahman, senior immunologist and science communicator, University of Cambridge, comments: "This study is an elegant example of how single‑cell profiling can uncover previously hidden cell types that only appear under specific physiological conditions — in this case, ageing. The next critical steps are to demonstrate whether these age‑associated macrophages are drivers of inflammaging or markers of tissue change, and to validate comparable populations in human tissue. That distinction matters for developing therapeutics."
Conclusion
The discovery of a novel macrophage subtype in the visceral fat of aged mice advances our understanding of how the immune system and adipose tissue change with age. These cells exhibit gene signatures consistent with inflammaging and lipid regulation, and their emergence only in older animals suggests they may contribute to chronic, age‑related inflammation. Further work is needed to determine relevance to humans and potential for targeted therapies to mitigate age‑associated inflammatory diseases.
Source: nature
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