ArticleAging2016
Aging of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells.
Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
223 citing papers in PubMed, 1 synthesis or guideline pooled it, 339 citations in OpenAlex.
- Markers of the ageing macrophage: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- Senotypes define the diverse landscape of senescent cells.Nature aging · 2026Review
- Article
- Limitations of the p16-3MR mouse model for detecting and eliminating senescent cells.EMBO reports · 2026Article
- Tumor Microenvironment Hijacks and Accelerates a Physiological Myeloid Senescence Signature Associated with Pan-Cancer Immunosuppression and Prognostic Stratification.International journal of molecular sciences · 2026Article
- Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Cellular Senescence in Skeletal Muscle Aging.Endocrinology and metabolism (Seoul, Korea) · 2026Review
- Glycative Stress Disrupts the Mitochondrial-Lysosome Axis and Promotes Geroconversion in Aging Cardiomyocytes.Aging cell · 2026Article
- The Role of Cellular Senescence in Oral Health and Disease.International journal of molecular sciences · 2026Review
- Senescent fibroblasts in aging and pulmonary fibrosis.Frontiers in aging · 2026Review
- Impaired intestinal cell proliferation parallels increased senescence after burn injury in aged mice.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.Frontiers in immunology · 2026Review
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Review
- Age-related severity of nontuberculous mycobacterial lung disease is mediated by aberrant macrophage responses and lung microbial dysbiosis.The Journal of infection · 2025Article
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- Intranasal delivery of DPSC-derived small extracellular vesicles-encased phloroglucinol attenuates non-motor and motor deficits and promotes neurogenesis in an in vivo rat model of Parkinson's disease.Stem cell research & therapy · 2025Article
- Senescent macrophages in tumor: phenotypes, roles, and interventions.Cell death & disease · 2025Review
163 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescent cells (SCs) have been considered a source of age-related chronic sterile systemic inflammation and a target for anti-aging therapies. To understand mechanisms controlling the amount of SCs, we analyzed the phenomenon of rapid clearance of human senescent fibroblasts implanted into SCID mice, which can be overcome when SCs were embedded into alginate beads preventing them from immunocyte attack. To identify putative SC killers, we analyzed the content of cell populations in lavage and capsules formed around the SC-containing beads. One of the major cell types attracted by secretory factors of SCs was a subpopulation of macrophages characterized by p16(Ink4a) gene expression and β-galactosidase activity at pH6.0 (β-gal(pH6)), thus resembling SCs. Consistently, mice with p16(Ink4a) promoter-driven luciferase, developed bright luminescence of their peritoneal cavity within two weeks following implantation of SCs embedded in alginate beads. p16(Ink4a)/β-gal(pH6)-expressing cells had surface biomarkers of macrophages F4/80 and were sensitive to liposomal clodronate used for the selective killing of cells capable of phagocytosis. At the same time, clodronate failed to kill bona fide SCs generated in vitro by genotoxic stress. Old mice with elevated proportion of p16(Ink4a)/β-gal(pH6)-positive cells in their tissues demonstrated reduction of both following systemic clodronate treatment, indicating that a significant proportion of cells previously considered to be SCs are actually a subclass of macrophages. These observations point at a significant role of p16(Ink4a)/β-gal(pH6)-positive macrophages in aging, which previously was attributed solely to SCs. They require re-interpretation of the mechanisms underlying rejuvenating effects following eradication of p16(Ink4a)/β-gal(pH6)-positive cells and reconsideration of potential cellular target for anti-aging treatment.
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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.