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Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Open accessAbstract
Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, and apoptotic resistance in multiple organs due to various stressors. Excessive accumulation of senescent cells in numerous tissues leads to multiple chronic diseases, tissue dysfunction, age-related diseases and organ ageing. Immune cells can remove senescent cells. Immunaging or impaired innate and adaptive immune responses by senescent cells result in persistent accumulation of various senescent cells. Although senolytics—drugs that selectively remove senescent cells by inducing their apoptosis—are recent hot topics and are making significant research progress, senescence immunotherapies using immune cell-mediated clearance of senescent cells are emerging and promising strategies to fight ageing and multiple chronic diseases. This short review provides an overview of the research progress to date concerning senescent cell-caused chronic diseases and tissue ageing, as well as the regulation of senescence by small-molecule drugs in clinical trials and different roles and regulation of immune cells in the elimination of senescent cells. Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that excessive senescent cells drive ageing and chronic diseases, and that immune-mediated clearance by macrophages, NK cells, cytotoxic T cells, and dendritic cells is a promising anti-ageing strategy. It surveys senolytics and small-molecule drugs in preclinical and clinical development and outlines immune mechanisms and future directions for senescence immunotherapy.
Key findings
- Senescent cells accumulate with age and causally contribute to tissue dysfunction, organ ageing, and chronic diseases including cardiovascular disease, cancer, neurodegenerative diseases, and osteoarthritis; immune cells can remove them, but immunosenescence and impaired innate/adaptive responses promote persistent accumulation.
- Senescence immunotherapy is emerging as an alternative or complement to senolytics: macrophages, NK cells, cytotoxic T cells, and dendritic cells recognize distinct senescent-cell ligands, such as NKG2D ligands MICA/ULBP2 on senescent cells, while HLA-E–NKG2A interaction inhibits NK/CD8+ T-cell clearance.
- Small molecules and senolytics show reported benefits: dasatinib plus quercetin (D + Q) eliminates senescent cells in human adipose tissue and skin and improves physical function in idiopathic pulmonary fibrosis; nicotinamide mononucleotide (NMN) was safe after single oral administration in healthy men; topical rapamycin reduced p16 expression in human skin; metformin has entered multiple clinical trials including MILES and TAME.
- In human immune ageing, supercentenarians older than 110 years had increased CD4+ cytotoxic T lymphocytes (~25.3% of total T cells) versus only 2.8% in young controls (~50–80 year olds), with a dramatic reduction in B-cell number compared with controls.
Methods
- Narrative review synthesizing preclinical animal models, human samples, mechanistic studies, and clinical trials; no systematic review or meta-analysis is described.
- Main analysis is qualitative and organized around senescent-cell features, senescent-cell-driven diseases and tissue ageing, small-molecule regulation of senescence, and immune cell types involved in senescent-cell clearance.
- Clinical trial examples cited include NCT03151239 for NMN safety, NCT03103893 for topical rapamycin, the Metformin in Longevity Study (MILES), NCT02570672 for metformin and frailty, NCT02915198 for metformin in pre-diabetes and atherosclerotic cardiovascular disease, and the proposed TAME trial.
Limitations
- The paper states that the precise mechanism underlying senescent cell accumulation within tissues is still debatable, and it is unknown whether this is due to senescent cell increase exceeding immune clearance or immune cell dysfunction.
- The paper states that whether macrophages remove senescent cells in aged or diseased systems remains to be elucidated, and it remains extremely unknown whether and how dendritic cells eliminate apoptotic or senescent cells to prevent chronic diseases including atherosclerosis.
- The paper states that senescence immunotherapy is not cost-free and does have side effects, and future investigations are needed for personal ageing biomarkers, unique senescent-cell antigens or ligands, and inclusion of both genders; evident from the text, many proposed immunotherapies such as CAR-T/CAR-NK targeting senescent cells and anti-NKG2A strategies are still speculative or not yet established in clinical senescence settings.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although senolytics—drugs that selectively remove senescent cells by inducing their apoptosis—are recent hot topics and are making significant research progress, senescence immunotherapies using immune cell-mediated clearance of senescent cells are emerging and promising strategies to fight ageing and multiple chronic diseases.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Cellular senescence plays beneficial critical roles in numerous biological processes [5], such as tumor suppression [6,7], embryonic tissue remodeling [8] and wound healing after injury [9].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
What the sources say
- Not checked yetcites [5] Burton, 2014, Physiological and pathological consequences of cellular senescence, Cell Mol. Life Sci. source
- Not checked yetcites [6] Lin, 2010, Skp2 targeting suppresses tumorigenesis by arf-p53-independent cellular senescence, Nature source
- Not checked yetcites [7] Braig, 2005, Oncogene-induced senescence as an initial barrier in lymphoma development, Nature source
- Not checked yetcites [8] Canamero, 2013, Programmed cell senescence during mammalian embryonic development, Cell source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Immune cells can remove senescent cells.”
- Also stated in: § 3. Immunosurveillance of Senescent Cells · plain
“Generally, senescent cells can be removed by apoptosis and the immune system [121,122].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § 3. Immunosurveillance of Senescent Cells · plain
In the paper
“Immunaging or impaired innate and adaptive immune responses by senescent cells result in persistent accumulation of various senescent cells.”
- Also stated in: § 3. Immunosurveillance of Senescent Cells · plain
“Senescent cells recruit and make immune cells senescent and dysfunctional via SASP, leading to persistent and excessive accumulation of senescent cells [122].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
What the sources say
- Not checked yetcites [122] Prata, 2018, Senescent cell clearance by the immune system: Emerging therapeutic opportunities, Semin. Immunol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § 3. Immunosurveillance of Senescent Cells · plain
In the paper
“Senescent cells in patients with idiopathic pulmonary fibrosis (IPF) drive physical dysfunction [45].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [45] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, EBioMedicine source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Zhang et al. employed a senolytic cocktail of dasatinib plus quercetin (D + Q) to validate that senescent OLIG2- and NG2-expressing oligodendrocyte progenitor cells (OPCs) contribute to cognitive impairment in an AD mouse model [56].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [56] Zhang, 2019, Senolytic therapy alleviates aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an alzheimer’s disease model, Nat. Neurosci. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Senescence of the central nervous system (CNS) drives many neurodegenerative diseases [55], including Alzheimer’s disease (AD), Parkinson’s disease (PD) and other types of dementia (Table 1).”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [55] Kritsilis, M., V Rizou, R., Koutsoudaki, P.N., Evangelou, K., Gorgoulis, V.G., and Papadopoulos, D. (2018). Ageing, cellular senescence and neurodegenerative disease. Int. J. Mol. Sci., 19. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Cellular senescence traditionally impairs stem-cell function (also termed as stemness) [58].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [58] Golomb, 2015, Age-associated inflammation connects ras-induced senescence to stem cell dysfunction and epidermal malignancy, Cell Death Differ. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Mounting evidence from human samples and preclinical animal models shows that the excessive presence of senescent cells is a contributing cause of ageing, which is featured by a functional decline in multiple physiological systems [39,40].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“However, the senescence of specific cancer cells develops cancer stemness.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [2] Milanovic, 2018, Senescence-associated reprogramming promotes cancer stemness, Nature source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 25
- Probably not a substantial claim. 5
None of the sources cited for this claim have been checked yet.
In the paper
“However, excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18] and osteoarthritis [19].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
What the sources say
- Not checked yetcites [11] Baker, 2016, Naturally occurring p16(ink4a)-positive cells shorten healthy lifespan, Nature source
- Not checked yetcites [12] Childs, 2015, Cellular senescence in aging and age-related disease: From mechanisms to therapy, Nat. Med. source
- Not checked yetcites [13] Baker, 2011, Clearance of p16ink4a-positive senescent cells delays ageing-associated disorders, Nature source
- Not checked yetcites [14] Childs, 2017, Senescent cells: An emerging target for diseases of ageing, Nat. Rev. Drug Discov. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
- Rests on an assumption: Findings from animal models and preclinical studies of senescent cell clearance will translate to human ageing and chronic diseases.
- Rests on an assumption: Targeting or clearing senescent cells can be done safely without eliminating beneficial functions of acute or transient senescence.
None of the sources cited for this claim have been checked yet.
In the paper
“Cellular senescence is a cell state in which the cell-cycle is generally irreversibly stopped [1], with cell-cycle reentry being a plausible scenario under specific circumstances, particularly in tumor cells [2].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
What the sources say
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“p16Ink4a (encoded by the INK4a/ARF locus, also known as CDKN2a, hereafter referred to as p16)-induced senescence of mouse and human pancreatic beta cells also promotes insulin secretion [10].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
What the sources say
- Not checked yetcites [10] Helman, 2016, P16(ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion, Nat. Med. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, and apoptotic resistance in multiple organs due to various stressors.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
What the sources say
- Not checked yetcites [1] Gorgoulis, 2019, Cellular senescence: Defining a path forward, Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Excessive accumulation of senescent cells in numerous tissues leads to multiple chronic diseases, tissue dysfunction, age-related diseases and organ ageing.”
- Also stated in: § 1. Introduction · plain
“However, excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18] and osteoarthritis [19].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > Abstract
What the sources say
- Not checked yetcites [11] Baker, 2016, Naturally occurring p16(ink4a)-positive cells shorten healthy lifespan, Nature source
- Not checked yetcites [12] Childs, 2015, Cellular senescence in aging and age-related disease: From mechanisms to therapy, Nat. Med. source
- Not checked yetcites [13] Baker, 2011, Clearance of p16ink4a-positive senescent cells delays ageing-associated disorders, Nature source
- Not checked yetcites [14] Childs, 2017, Senescent cells: An emerging target for diseases of ageing, Nat. Rev. Drug Discov. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § 1. Introduction · plain
None of the sources cited for this claim have been checked yet.
In the paper
“There are two major types of cellular senescence: stress-induced premature cellular senescence [3] and replicative senescence due to a repeated cell cycle, which is usually mediated by telomere shortening [4].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
What the sources say
- Not checked yetcites [3] Liu, 2015, Impact of er stress-regulated atf4/p16 signaling on the premature senescence of renal tubular epithelial cells in diabetic nephropathy, Am. J. Physiol. Cell Physiol. source
- Not checked yetcites [4] Mao, 2012, Replicatively senescent cells are arrested in g1 and g2 phases, Aging source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Recently, cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS) was shown to recognize cytosolic DNA in senescent cells to produce cGAMP, which triggers the generation of SASP factors via stimulator of interferon genes (STING) and promotes paracrine senescence [35].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.1. Features of Cellular Senescence
What the sources say
- Not checked yetcites [35] Gluck, 2017, Innate immune sensing of cytosolic chromatin fragments through cgas promotes senescence, Nat. Cell Biol. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The first-in-human open-label pilot study indicates that D + Q directly eliminates senescent cells in human adipose tissue and skin [120] and significantly improves the physical function of participants with idiopathic pulmonary fibrosis [45].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.3. Regulation of Cellular Senescence and Consequent Tissue Ageing and Disorders
What the sources say
- Not checked yetcites [120] Hickson, 2019, Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, EBioMedicine source
- Not checked yetcites [45] Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study, EBioMedicine source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Senescent cells generally demonstrate an enlarged and flattened cell morphology [27] and expanded nucleoli [28,29], enhanced senescence-associated beta-galactosidase (SA-β-gal) activity [30], telomere shortening, elevation of the cyclin-dependent kinase inhibitor p16 [11,31] or p21 [32], macromolecular damage and metabolism dysfunction [1].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.1. Features of Cellular Senescence
What the sources say
- Not checked yetcites [27] Mammoto, 2019, Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through yap1, Aging source
- Not checked yetcites [28] Buchwalter, 2017, Nucleolar expansion and elevated protein translation in premature aging, Nat. Commun. source
- Not checked yetcites [29] Tiku, 2017, Small nucleoli are a cellular hallmark of longevity, Nat. Commun. source
- Not checked yetcites [30] Matthews, 2006, Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: Effects of telomerase and oxidative stress, Circ. Res. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Lipofuscin is an emerging and more sensitive biomarker than SA-β-gal activity for cellular senescence in vitro and in vivo.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.1. Features of Cellular Senescence
What the sources say
- Not checked yetcites [37] Evangelou, 2017, Robust, universal biomarker assay to detect senescent cells in biological specimens, Aging Cell. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Bussian et al. reported that clearance of p16+ senescent astrocytes and microglia using INKATTAC transgene restrains gliosis, super-phosphorylation of both soluble and insoluble tau resulting in neurofibrillary tangle deposition and degeneration of cortical and hippocampal neurons, thus restoring cognitive function.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 2. Cellular Senescence Causally Contributes to Ageing and Chronic Diseases > 2.2. Senescent Cells Drive Ageing and Various Chronic Diseases
What the sources say
- Not checked yetcites [18] Bussian, 2018, Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline, Nature source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cellular senescence accumulation usually arises from increased stresses-induced cellular senescence and reduction of senescent cell removal due to apoptosis evasion and/or immune system dysfunction.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 1. Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“DRP1-deficient macrophages present impaired efferocytosis in vivo and subsequently increased plaque necrosis in advanced atherosclerotic lesions of Western diet-fed LDLR knockout mice [147].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [147] Wang, 2017, Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages, Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Both macrophage and apoptotic or senescent cells control macrophage efferocytosis ability.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“These senescent tumor cells recruit innate immune cells, such as macrophages, leading to the eradication of senescent tumor cells and subsequent tumor regression [145].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [145] Xue, 2007, Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas, Nature source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Antibodies blocking CD47 reactivate efferocytosis of diseased vascular tissue without altering cellular apoptosis, as well as alleviate atherosclerosis in both the aortic sinus and en face of the aorta in multiple mouse models [148].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [148] Kojima, 2016, Cd47-blocking antibodies restore phagocytosis and prevent atherosclerosis, Nature source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Senescent cells recruit and make immune cells senescent and dysfunctional via SASP, leading to persistent and excessive accumulation of senescent cells [122].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells
What the sources say
- Not checked yetcites [122] Prata, 2018, Senescent cell clearance by the immune system: Emerging therapeutic opportunities, Semin. Immunol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“F4/80+ macrophages are also key players in the removal of senescent uterine cells after parturition to keep postpartum uterine functionality in wild-type mice and maintain the success rate of a second pregnancy in a preterm birth mouse model [135].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [135] Egashira, 2017, F4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus, Endocrinology source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Kang et al. demonstrated that CD4+ T cells require monocytes/macrophages but not NK cells, to remove pre-malignant senescent hepatocytes, subsequently blocking liver tumor development [130].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [130] Kang, 2011, Senescence surveillance of pre-malignant hepatocytes limits liver cancer development, Nature source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The impaired ability of macrophage efferocytosis would enhance atherogenesis [139,140,141] and atherosclerotic plaque instability [142,143,144].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [139] Proto, 2018, Regulatory t cells promote macrophage efferocytosis during inflammation resolution, Immunity source
- Not checked yetcites [140] Schrijvers, 2005, Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [141] Kojima, 2017, The role of efferocytosis in atherosclerosis, Circulation source
- Not checked yetcites [142] Seneviratne, 2017, Interferon regulatory factor 5 controls necrotic core formation in atherosclerotic lesions by impairing efferocytosis, Circulation source
- Not checked yetcites [143] Thorp, 2008, Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [144] Yurdagul, 2017, Mechanisms and consequences of defective efferocytosis in atherosclerosis, Front. Cardiovasc Med. source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Excessive and persistent accumulation of different senescent cells drives unique ageing and chronic disease development.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 4. Conclusions and Future Perspectives
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“p53-expressing senescent liver tumor cells recruit NK cells by inducing the chemokine CCL2 but not CCL3, CCL4 or CCL5, in senescent tumor cells without affecting the ligand expression of RAE-1 proteins in the tumor cells [153].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [153] Iannello, 2013, P53-dependent chemokine production by senescent tumor cells supports nkg2d-dependent tumor elimination by natural killer cells, J. Exp. Med. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Thus, apoptotic cells without CDKN2B impair macrophages efferocytosis and result in the development of advanced atherosclerotic plaques with large necrotic cores.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [149] Kojima, 2014, Cyclin-dependent kinase inhibitor 2b regulates efferocytosis and atherosclerosis, J. Clin. Investig. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the adoptive constitution of engineered specific CAR-CD8+ T cells selectively targeting FAP notably alleviates cardiac fibrosis and reverses both systolic and diastolic cardiac function in angiotensin II and phenylephrine-treated mice [134].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [134] Aghajanian, 2019, Targeting cardiac fibrosis with engineered t cells, Nature source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“mice with defects in granule exocytosis accumulate senescent stellate cells and display stronger liver fibrosis in response to a fibrogenic agent [131].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [131] Sagiv, 2013, Granule exocytosis mediates immune surveillance of senescent cells, Oncogene source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Notably, ligands or antigens to activate the receptors NKG2D and DNAM-1 or ligands HLA-E for the inhibitory receptor NKG2A, have demonstrated expression in senescent cells.”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NK cell activation by polyinosinic-polycytidylic acid [152] decreases the senescent cell number in the liver in vivo, leading to reduced liver fibrosis [20].”
§ Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases > 3. Immunosurveillance of Senescent Cells > 3.2. Immunotherapy to Eliminate Senescent Cells
What the sources say
- Not checked yetcites [152] Radaeva, 2006, Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in nkg2d-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners, Gastroenterology source
- Not checked yetcites [20] Krizhanovsky, 2008, Senescence of activated stellate cells limits liver fibrosis, Cell source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Findings from animal models and preclinical studies of senescent cell clearance will translate to human ageing and chronic diseases.
“Mounting evidence indicates that immunotherapy targeting senescent cells combats ageing and chronic diseases and subsequently extends the healthy lifespan.”
The paper relies on this without support.
Targeting or clearing senescent cells can be done safely without eliminating beneficial functions of acute or transient senescence.
“Usually, sudden or acute senescence will exert beneficial functions such as anti-fibrosis [20] and wound healing [21].”
The paper relies on this without support.
Maintaining immune system function is sufficient to prevent or reduce pathological accumulation of senescent cells.
“A study investigating human ageing at the individual level by frequent sampling and prolonged deep molecular profiling indicates that immune pathways are one of the significant pathways that alter with age [38].”
The paper relies on this without support.
Selectivity and efficiency of cytotoxic T cells decline with age.
“However, the selectivity and efficiency of cytotoxic T cells decline with age.”
The paper relies on this without support.
Senescent cells are beneficial in the short term.
“Because senescent cells are also beneficial in the short term, the homeostasis of senescent cells is critical for healthy ageing.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“On the other hand, immune cell-mediated clearance of senescent cells is emerging as a promising strategy to fight multiple chronic diseases and aging.349”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [349]
In the citing paper
“the mechanisms underlying this immune escape closely mirror those utilized by tumor cells, offering valuable insights and a conceptual framework for the development of immune-based senotherapeutic strategies57,58.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [58]
In the citing paper
“the mechanisms underlying this immune escape closely mirror those utilized by tumor cells, offering valuable insights and a conceptual framework for the development of immune-based senotherapeutic strategies57,58.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [58]
Citations
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“Moreover, rapamycin, the US Food and Drug Administration-approved mTOR inhibitor, has been shown to extend the median and maximal lifespans of both male and female genetically heterogeneous mice [99].”
BackgroundClearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1×
“However, excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18] and o…”
BackgroundCellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225 · cited 8×
“Senescent cells generally demonstrate an enlarged and flattened cell morphology [27] and expanded nucleoli [28,29], enhanced senescence-associated beta-galactosidase (SA-β-gal) activity [30], telomere shortening, elevation of the cyclin-dependent kinase inhibitor p16 [11,31] or p21 [32], macromolecular damage and meta…”
BackgroundInfluentialCar t cell immunotherapy for human cancer
June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S., & Milone, M. C. (2018) · Science · doi:10.1126/science.aar6711 · Cited by 3,207 · cited 1×
“Reinstructing cytotoxic T cells to identify specific antigens on cancer cells using either a modified T-cell receptor or a chimeric antigen receptor (CAR) has been successfully used for specific cancer therapies [156].”
BackgroundNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
The role of senescent cells in ageing
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Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
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“These senescent tumor cells recruit innate immune cells, such as macrophages, leading to the eradication of senescent tumor cells and subsequent tumor regression [145].”
BackgroundCellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363 · cited 1×
“However, excessive accumulation of senescent cells causally shortens the healthy lifespan [11] and drives organ ageing [12], age-related organ deterioration/disorders [13,14], tissue dysfunction and chronic diseases, including cardiovascular diseases (CVDs) [15,16], cancer [2], neurodegenerative diseases [17,18] and o…”
BackgroundSenolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287 · cited 1×
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BackgroundThe ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
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Items 101–197 of 197
Role of Senescence in Tumorigenesis and Anticancer Therapy
Stoczyńska-Fidelus, E., Węgierska, M., Kierasińska, A., Ciunowicz, D., & Rieske, P. (2022) · Journal of Oncology · doi:10.1155/2022/5969536 · Cited by 15
“It is worth mentioning that the indicated ligands are more often found in the membrane of neoplastic cells than in normal cells [86, 87].”
BackgroundCellular senescence and cell therapy in cardiovascular diseases
Chang, D., Wang, J., Zhu, S., Shentu, Y., Wang, Y., Zhu, P., & Ōno, M. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04731-6 · Cited by 13
“Interestingly, immune cells act as a double-edged sword during the pathological process of HF because they also benefit HF through their clearance function [10].”
Sharma, A. R., Chatterjee, S., Lee, Y., & Lee, S. (2023) · Aging and Disease · doi:10.14336/ad.2023.00903 · Cited by 15
“An abundance of senescent cells has been shown to have a causative effect on the acceleration of tissue aging, potentially leading to chronic illnesses and cellular senescence [53].”
BackgroundZhang, M., Wei, J., Sun, Y., He, C., Ma, S., Pan, X., & Zhu, X. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.03.008 · Cited by 15
“Immune cell-mediated senescent cell clearance is recognized as a potentially effective approach for combating various chronic ailments and aging process [192–194].”
McGrath, M. K., Abolhassani, A., Guy, L., Elshazly, A. M., Barrett, J. T., Mivechi, N. F., Gewirtz, D. A., & Schoenlein, P. V. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1298423 · Cited by 13
“These actions prevent the elimination of senescent cells, resulting in their accumulation in tissues, which ultimately contributes to chronic in fl ammation, cancer progression and metastasis (138, 139).”
BackgroundKwon, H. J., Hahn, K. R., Nam, S. M., Yoon, Y. S., Moon, S. M., Hwang, I. K., & Kim, D. W. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105552 · Cited by 12
Sharma, R., Kumar, R., Sharma, A., Goel, A., & Padwad, Y. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.01.425058 · Cited by 11
“In addition, it is also increasingly recognized that the accumulation of oxi-inflammatory stress in cells as well as functional inefficacy of the immune system play a critical role in the development and progression of cellular senescence and its known effects during aging (Song et al 2020).”
BackgroundLiu, F., & Cai, H. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1583267 · Cited by 10
A Cellular Senescence-Centric Integrated Approach to Understanding Organismal Aging
Sharma, R., & Diwan, B. (2022) · Current Aging Science · doi:10.2174/1874609815666220914104548 · Cited by 9
Ljubič, M., Prašnikar, E., Perdih, A., & Borišek, J. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00249 · Cited by 10
Sfera, A., Osorio, C. P., Hazan, S., Kozlakidis, Z., Maldonado, J. C., del Campo, C. M. Z.-M., Anton, J. J., Rahman, L., Andronescu, C. V., & Nicolson, G. L. (2022) · Endocrines · doi:10.3390/endocrines3040058 · Cited by 9
Spatiotemporal changes of tissue glycans depending on localization in cardiac aging
Itakura, Y., Hasegawa, Y., Kikkawa, Y., Murakami, Y., Sugiura, K., Nagai‐Okatani, C., Sasaki, N., Umemura, M., Takahashi, Y., Kimura, T., et al. (2023) · Regenerative Therapy · doi:10.1016/j.reth.2022.12.009 · Cited by 9
Immunity in the Progeroid Model of Cockayne Syndrome: Biomarkers of Pathological Aging
Zayoud, K., Chikhaoui, A., Kraoua, I., Tebourbi, A., Najjar, D., Ayari, S., Safra, I., Kraiem, I., Turki, I., Menif, S., et al. (2024) · Cells · doi:10.3390/cells13050402 · Cited by 10
“Thus, the immune system loses its effectiveness, and therefore, it does not properly eliminate damaged cells [9,10].”
BackgroundRejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells
Wang, X., Zhang, C., Su, J., Ren, S., Wang, X., Zhang, Y., Yuan, Z., He, X., Wu, X., Li, M., et al. (2025) · Aging and disease · doi:10.14336/ad.2024.0579 · Cited by 8
“Additionally, NK cells can exert their effects by activating the interaction between their own receptors and ligands on senescent cells, thereby releasing cytotoxic particles such as granzyme and perforin [104].”
Aging and lung diseases: Unraveling mechanisms and therapeutic targets
Zhou, Y., Chen, G., Li, X., Li, X., Lin, Z., Liu, L., Pu, D., Chen, J., Chen, Y., Lin, Z., et al. (2025) · Chinese Medical Journal - Pulmonary and Critical Care Medicine · doi:10.1016/j.pccm.2025.11.005 · Cited by 10
“26 Senescence of immune cells could lead to the impairment of the immune surveillance ability, which is responsible for the accumulation of senescent cells in the lungs.”
DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat
Boughey, H., Jurga, M., & El‐Khamisy, S. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116011 · Cited by 10
Inflammaging and Immunosenescence in the Post‐COVID Era: Small Molecules, Big Challenges
Francavilla, F., Intranuovo, F., Spada, G. L., Lacivita, E., Catto, M., Graps, E. A., & Altomare, C. (2024) · ChemMedChem · doi:10.1002/cmdc.202400672 · Cited by 13
Inflammaging and Cardiovascular Risk in Old Women
Moscucci, F., Baratta, F., Bucciarelli, V., Mattioli, A. V., Pinti, M., Zanini, G., Sciomer, S., Gallina, S., Piccirillo, G., & Desideri, G. (2025) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-025-00758-1 · Cited by 8
“…of senescent cells secreting pro-inflammatory mediators, which have the potential to propagate the senescent phenotype to neighboring cells [ 14 ] promoting age-related diseases [ 15 ]; (ii) reactive oxygen species (ROS) and other agents can cause nuclear DNA damage, often associated with…”
Advances in biomarkers and diagnostic significance of organ aging
Chen, Y., Li, J., Liu, X., Geng, Z., Xu, K., & Su, J. (2023) · Fundamental Research · doi:10.1016/j.fmre.2023.03.009 · Cited by 9
“Several hallmarks of aging have been identified as key markers for the diagnosis of aging diseases, and the selection of biological markers for assessing organ aging status uses biological age to accurately assess the degree of aging in individuals [ 8 , 9 ].”
Hepatic Fibrosis and Liver Cancer
Anton, A., Friedman, S. L., & Cogliati, B. (2025) · Seminars in Liver Disease · doi:10.1055/a-2779-4937 · Cited by 10
Cell Senescence and the Genetics of Melanoma Development
Constantinou, S. M., & Bennett, D. C. (2024) · Genes Chromosomes and Cancer · doi:10.1002/gcc.23273 · Cited by 7
“SASP factors can often promote the immune clearance of senescent cells [68].”
Zhou, Y., & Yan, R. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05111-0 · Cited by 6
“Natural killer (NK) cells, as important innate immune cells, participate in the immune monitoring of aging cells and have a certain association with neurodegenerative diseases [4, 5].”
Immunotherapies for Aging and Age-Related Diseases: Advances, Pitfalls, and Prospects
Yang, M., Wu, S., Zhang, J., Lu, L., Deng, D., Xia, Q., Lovell, J. F., Shi, X., & Jin, H. (2025) · Research · doi:10.34133/research.0866 · Cited by 7
“Under physiological conditions, the immune surveillance sys-tem controls the number of senescent cells via the cytotoxicity of lymphocytes and the phagocytosis of macrophages and granulocytes [ 27 ].”
Reading the immune clock: a machine learning model predicts mouse immune age from cellular patterns
Sim, H. B., Jang, J.-H., Mun, S., Ramos, S., Park, D.-H., Choi, Y.-J., Han, J., Lee, J.-B., Chung, H. S., Lee, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67393-1 · Cited by 6
Effect of senolytic drugs in young female mice chemically induced to estropause
Ávila, B. M., Zanini, B. M., Luduvico, K. P., Oliveira, T. L., Hense, J. D., Garcia, D. N., Prosczek, J. B., Stefanello, F. M., Cruz, P. H. F. D., Giongo, J. L., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123073 · Cited by 6
Escriche‐Navarro, B., Garrido, E., Trujillo, S. C., Labernadie, A., Sancenón, F., García‐Fernández, A., & Martínez‐Máñez, R. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c17748 · Cited by 6
Cellular senescence and lung cancer prognosis
Asaithamby, A., Shay, J. W., & Minna, J. D. (2022) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-678 · Cited by 6
“As a result, senescent cells are cleared by the leukocytes belonging to the innate immune system in a context-dependent manner (16,17).”
A multiscale orchestrated computational framework to reveal emergent phenomena in neuroblastoma
Borau, C., Wertheim, K. Y., Hervás-Raluy, S., Sainz‐DeMena, D., Walker, D., Chisholm, R., Richmond, P., Varella, V., Viceconti, M., Montero, A., et al. (2023) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2023.107742 · Cited by 6
The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians.
Montella, F., Lopardo, V., Cattaneo, M., Carrizzo, A., Vecchione, C., Ciaglia, E., & Puca, A. A. (2021) · PubMed Central · doi:10.37825/2239-9754.1029 · Cited by 6
“As the excessive senescent cells accumulation represents one of the pillars of ageing and chronic diseases [83,84], AAV-LAV-BPIFB4 treatment”
High content imaging for monitoring signalling dynamics in single cells
Garner, K. (2020) · Journal of Molecular Endocrinology · doi:10.1530/jme-20-0169 · Cited by 6
Induction of senescence renders cancer cells highly immunogenicPreprint
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Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming
Zhang, W., Song, S., Zhang, Y., Pan, Y., Hu, D., & Wang, Y. (2026) · npj Aging · doi:10.1038/s41514-026-00355-z · Cited by 6
Sendotypes predict worsening renal function in chronic kidney disease patients
McLarnon, T., Watterson, S., McCallion, S., Cooper, E., English, A. R., Kuan, Y., Gibson, D. S., Murray, E. K., McCarroll, F., Zhang, S., et al. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70279 · Cited by 5
“20 Senescent cells can also chemo-attract specific immune cells which direct their clearance; however, in dysfunctional tissue, senescent cells can accumulate and evade both innate and adaptive immune responses, 21,22 allowing them to continue promoting inflammation via SASP.”
Xu, T., Xia, R., He, F., Dong, E.-H., Shen, J., Xu, C.-C., Ji, M., & Xu, Q. L. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e13217 · Cited by 6
“Physiological characteristics of frailty can be explained by increased inflammatory factors [37,38].”
BackgroundMitra, S., Gera, R., Sundheimer, J. K., Lemee, M., Wahlberg, L. U., Linderoth, B., Eriksdotter, M., & Behbahani, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169011 · Cited by 5
OR2H2 Activates CAMKKβ–AMPK–Autophagy Signaling Axis and Suppresses Senescence in VK2/E6E7 Cells
Kim, J. M., Dziobaka, S., Yoon, Y. E., Lee, H. L., Jeong, J. H., Lee, I.-R., Weidinger, D., Yang, C., Kim, D., Yalcin, G., et al. (2023) · Pharmaceuticals · doi:10.3390/ph16091221 · Cited by 5
“Accumulation of senescent cells contributes to chronic diseases, tissue dysfunction, age-related ailments, and organ aging [24]. age-related ailments, and organ aging [24].”
BackgroundAfsar, A., & Li, Z. (2024) · Biology · doi:10.3390/biology13030185 · Cited by 4
“However, SCs can also interact with immune cells to evade elimination [128,129].”
BackgroundEntwistle, A., Walker, S., Knecht, A. K., Strum, S. L., Shah, A. A., Podgoreanu, M. V., Pustavoitau, A., Mitin, N., & Williams, J. B. (2024) · Cardiology and Cardiovascular Medicine · doi:10.26502/fccm.92920387 · Cited by 5
Impacts of Radiation on Metabolism and Vascular Cell Senescence
Abe, J., Chau, K., Mojiri, A., Wang, G., Oikawa, M., Samanthapudi, V. S. K., Osborn, A. M., Ostos-Mendoza, K. C., Mariscal-Reyes, K. N., Mathur, T., et al. (2025) · Antioxidants and Redox Signaling · doi:10.1089/ars.2024.0741 · Cited by 4
“Radiation induces mitochondrial dysfunction and cellular senescence in immune cells, a phenomenon known as immu-nosenescence, which impairs both innate and adaptive immunity and contributes to the progression of CVD (Song et al., 2020).”
Zhu, X., Liu, Q., Patterson, A. D., Sharma, A. K., Amin, S., Cohen, S. M., Gonzalez, F. J., & Peters, J. M. (2023) · Metabolites · doi:10.3390/metabo13080936 · Cited by 4
Song, G., Wu, H., Chen, H., Zhang, S., Hu, Q., Lai, H., Fuller, C., Yang, G., & Chi, H. (2024) · Current Alzheimer Research · doi:10.2174/0115672050314171240527064514 · Cited by 4
G protein coupled receptor in apoptosis and apoptotic cell clearance
Li, X., Li, C., Kang, Y., Zhang, R., Li, P., Zheng, Q., Wang, H., Xiao, H., & Yuan, L. (2024) · FASEB BioAdvances · doi:10.1096/fba.2024-00067 · Cited by 4
Choroidal macrophages in homeostasis, aging and age-related macular degeneration
Khan, A. H., & Mulfaul, K. (2024) · Experimental Eye Research · doi:10.1016/j.exer.2024.110159 · Cited by 4
Role of BPIFB4 in Immune System and Cardiovascular Disease: the Lesson from Centenarians
Montella, F., Lopardo, V., Cattaneo, M., Carrizzo, A., Vecchione, C., Ciaglia, E., & Puca, A. A. (2022) · Translational Medicine UniSa · doi:10.37825/2239-9747.1024 · Cited by 4
Natural killer cell-based senotherapy: a promising strategy for healthy aging
中澤務, Yamanishi, R., Morimoto, T., & Matusda, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1737572 · Cited by 3
“Furthermore, targeting immunosenescence and SNCs has emerged as a pivotal therapeutic strategy for promoting and maintaining healthy aging (111, 167, 168).”
Engineering Immune Cell to Counteract Aging and Aging‐Associated Diseases
Guo, J., Lei, L., Jin, Y., Su, L., Cui, S., & Shi, L. (2026) · Advanced Science · doi:10.1002/advs.202521776 · Cited by 3
“In a human trial, autologous NK cell infusion combined with oral metformin and rapamycin significantly reduced circulating p16 and IL-6 for 6-12 months [ 130 ].”
Rastgoo, S., Pourvali, K., Raeissadat, S. A., Eslamian, G., & Zand, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1570441 · Cited by 3
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“Fundamentally, muscle aging is the core cause of sarcopenia [8], but unfortunately, no clinical drugs capable of delaying muscle aging have been developed yet.”
Advancing Alzheimer's disease treatment: A literature review on senolytic intervention
Onuh, V. C. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251376540 · Cited by 2
“9,41,42 This strategy aligns with the broader goal of reducing multimor-bidity and increasing healthspan, potentially yielding substantial societal and economic bene fi ts.”
Olinger, B., & Basisty, N. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103254 · Cited by 2
Decline of chaperone-mediated autophagy in aging impairs macrophage clearance of senescent cells
Sereda, R., Lindenau, K. L., Díaz, A., Liu, Z., Santiago‐Fernández, O., Khawaja, R. R., Cutler, R. R., Calyeca, J., McCabe, M., Durand, S., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01240-w · Cited by 4
Integrating cuproptosis and immunosenescence: A novel therapeutic strategy in cancer treatment
Firouzjaei, A. A., & Aghaee‐Bakhtiari, S. H. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.101983 · Cited by 4
“This inhibition can also lead to the accumulation of inflammatory proteins, resulting in an exaggerated inflammatory response that can further damage tissues [41 – 43].”
Dietary patterns and the neoplastic‐prone tissue landscape of old age
Marongiu, F., & Laconi, E. (2020) · Aging and Cancer · doi:10.1002/aac2.12021 · Cited by 2
Cell Level- Modeling of Aging and Rejuvenation
Koptyug, A. V., Суховей, Ю. Г., Костоломова, Е. Г., Unger, I., & Va, K. (2023) · OBM Geriatrics · doi:10.21926/obm.geriatr.2304263 · Cited by 1
Influence of Altered Gut Microbiota in Cellular Senescence
Ponnusamy, B., & Jayaraman, S. (2024) · Springer eBooks · doi:10.1007/978-981-99-8803-7_6 · Cited by 1
Kawakami, S., Ninomiya, R., & Maeda, Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126332 · Cited by 2
“…biological aging would progress due to a decline in immune function, leading to the development of lifestyle-related diseases, etc. [9]. normal circumstances, biological aging would progress due to a decline in immune function, leading to the development of lifestyle-related diseases, etc. [9].”
BackgroundПЕПТИДНАЯ РЕГУЛЯЦИЯ КЛЕТОЧНОГО СТАРЕНИЯ
Ivko, O. M. (2024) · Успехи геронтологии · doi:10.34922/ae.2024.37.5.004 · Cited by 1
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Senescent cell accumulation is associated with T-cell imbalance in the skin
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Biological Age Acceleration and All-Cause Mortality in Moderate to Severe Aortic Valve Stenosis
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Cellular Senescence in Skin Wound Repair: Dual Roles and Senotherapeutic Interventions
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The role of targeting cell senescence in vascular diseases and its potential application
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A PILLAR OF CARDIOVASCULAR DISEASES: INFLAMMAGING
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ТЕОРИЯ ВОЗРАСТНОЙ ЖИЗНЕСПОСОБНОСТИ В ГЕРИАТРИЧЕСКОЙ МЕДИЦИНЕ
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The Senescence-Malignancy Axis: An Inflammaging Perspective
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Metadata
- Authors
- Song, P., An, J., & Zou, M.-H.
- Affiliations
- Georgia State University (US)
- Corresponding author
- Song, Ping
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2020-03-10
- Volume
- 9
- Issue
- 3
- Pages
- 671
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC7140645
- OpenAlex
- W3011483812
- Semantic Scholar
- 533bd613fedce791195cd41b29206c4ed982619d
- Cited by
- 198
- References
- 164
- Citations by year
- 2026: 22 · 2025: 37 · 2024: 40 · 2023: 23 · 2022: 38 · 2021: 24 · 2020: 12
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Foundation for the National Institutes of Health (AG047776, HL089920, HL110488, HL128014, HL132500, HL137371, HL140954, CA213022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- senescent cells, immune clearance, immunosenescence, senolytics, aging, chronic disease, tissue aging, immune cells, apoptosis, healthspan, small molecule drugs
- MeSH terms
- Aging, Chronic Disease, Humans, Immunotherapy, Cellular Senescence
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