ArticleAging cell2015
The aged nonhematopoietic environment impairs natural killer cell maturation and function.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
The trial behind it
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
38 citing papers in PubMed, 66 citations in OpenAlex.
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.Frontiers in immunology · 2026Review
- Aging and vaccines: impact of immunosenescence and inflammaging in vaccine response.Frontiers in aging · 2026Review
- Review
- Phenotypes, mechanisms, and therapeutic strategies of natural killer cell immunosenescence.Immunity & ageing : I & A · 2025Review
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Immunosenescence promotes cancer development: from mechanisms to treatment strategies.Cell communication and signaling : CCS · 2025Review
- Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.International journal of biological sciences · 2025Review
- The infection-microbiome-immunity axis in bladder cancer: mechanistic insights and therapeutic perspectives.Frontiers in immunology · 2025Review
- Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process.Immunity & ageing : I & A · 2024Article
- DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.Immunologic research · 2024Article
- NK cell transfer overcomes resistance to PD-(L)1 therapy in aged mice.Experimental hematology & oncology · 2024Article
- Natural Killer Cells as a Further Insight into the Course of Chronic Obstructive Pulmonary Disease.Biomedicines · 2024Article
- Impact and potential value of immunosenescence on solid gastrointestinal tumors.Frontiers in immunology · 2024Review
- Considerations and Approaches for Cancer Immunotherapy in the Aging Host.Cancer immunology research · 2023Review
- Review
- Review
- Implications of the Immune Landscape in COPD and Lung Cancer: Smoking Versus Other Causes.Frontiers in immunology · 2022Review
- Regenerative Medicine and the Hope for a Cure.Clinics in chest medicine · 2021Review
- Aging and Options to Halt Declining Immunity to Virus Infections.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells are critical in eliminating tumors and viral infections, both of which occur at a high incidence in the elderly. Previous studies showed that aged NK cells are less cytotoxic and exhibit impaired maturation compared to young NK cells. We evaluated whether extrinsic or intrinsic factors were responsible for the impaired maturation and function of NK cells in aging and whether impaired maturation correlated with functional hyporesponsiveness. We confirmed that aged mice have a significant decrease in the frequency of mature NK cells in all lymphoid organs. Impaired NK cell maturation in aged mice correlated with a reduced capacity to eliminate allogeneic and B16 tumor targets in vivo. This could be explained by impaired degranulation, particularly by mature NK cells of aged mice. Consistent with impaired aged NK cell maturation, expression of T-bet and Eomes, which regulate NK cell functional maturation, was significantly decreased in aged bone marrow (BM) NK cells. Mixed BM chimeras revealed that the nonhematopoietic environment was a key determinant of NK cell maturation and T-bet and Eomes expression. In mixed BM chimeras, NK cells derived from both young or aged BM cells adopted an 'aged' phenotype in an aged host, that is, were hyporesponsive to stimuli in vitro, while adopting a 'young' phenotype following transfer in young hosts. Overall, our data suggest that the aged nonhematopoietic environment is responsible for the impaired maturation and function of NK cells. Defining these nonhematopoietic factors could have important implications for improving NK cell function in the elderly.
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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.