ArticleNature immunology2022
Aging disrupts circadian gene regulation and function in macrophages.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Bone aging: a paradigm of multiscale degeneration and targeted rejuvenation.Bone research · 2026Review
- Noncircadian BMAL1-YAP activity amplifies persistent inflammation in aged epidermis.Nature aging · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Circadian regulation of cardiovascular function: from physiology to clinical implications.Genome medicine · 2026Review
- Obesity-driven extracellular vesicle signaling in cancer: mechanistic insights and clinical implications.Oncogenesis · 2026Review
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Age-Associated Senescence of Decidual Macrophages: A Key Mediator of Adverse Pregnancy Outcomes in Advanced Maternal Age.Aging cell · 2026Article
- Angiotensin-Converting Enzyme 2 Overexpression Protects Heart from Aging-Induced Injury in C57BL/6 Mice.International journal of molecular sciences · 2026Article
- OCT4-driven PER1 activation promotes odontogenic differentiation in senescent SCAP spheres.International journal of oral science · 2026Article
- Redox rhythms promote fitness by modulating ageing-dependent reprogramming.Nature metabolism · 2026Article
- The clockwork macrophage: Timing in innate immunity.Biomedical journal · 2026Review
- Immunosenescence and Cancer: Cellular Aging Programs That Reshape Antitumor Immunity.Immune network · 2026Review
- Article
- The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer.Cancers · 2026Review
- Photothermal-Immunomodulatory Hydrogel Reinforced by TiAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- By dawn or dusk-how circadian timing rewrites bacterial infection outcomes.FEBS letters · 2026Review
- DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence.Nature communications · 2026Article
- Quantifying Information Exchange Between Cells in Inflammaging.Bioengineering (Basel, Switzerland) · 2026Article
- Respiratory virus immune response in the aged host.Immunity & ageing : I & A · 2026Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Aging is characterized by an increased vulnerability to infection and the development of inflammatory diseases, such as atherosclerosis, frailty, cancer and neurodegeneration. Here, we find that aging is associated with the loss of diurnally rhythmic innate immune responses, including monocyte trafficking from bone marrow to blood, response to lipopolysaccharide and phagocytosis. This decline in homeostatic immune responses was associated with a striking disappearance of circadian gene transcription in aged compared to young tissue macrophages. Chromatin accessibility was significantly greater in young macrophages than in aged macrophages; however, this difference did not explain the loss of rhythmic gene transcription in aged macrophages. Rather, diurnal expression of Kruppel-like factor 4 (Klf4), a transcription factor (TF) well established in regulating cell differentiation and reprogramming, was selectively diminished in aged macrophages. Ablation of Klf4 expression abolished diurnal rhythms in phagocytic activity, recapitulating the effect of aging on macrophage phagocytosis. Examination of individuals harboring genetic variants of KLF4 revealed an association with age-dependent susceptibility to death caused by bacterial infection. Our results indicate that loss of rhythmic Klf4 expression in aged macrophages is associated with disruption of circadian innate immune homeostasis, a mechanism that may underlie age-associated loss of protective immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.