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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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Cellular senescence drives age-dependent hepatic steatosis
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BackgroundFisetin is a senotherapeutic that extends health and lifespan
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“Usually, sudden or acute senescence will exert beneficial functions such as anti-fibrosis [20] and wound healing [21].”
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c-Jun overexpression in CAR T cells induces exhaustion resistance
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“In addition, β-hydroxybutyrate (β-HB) may mediate the effect of a ketogenic diet [113,114], intermittent fasting [115] or exercise [116] on healthspan extension or neuroregeneration because of its anti-inflammation [117], inhibition of vascular cell senescence [118] or immune activation by the formation and maintenanc…”
BackgroundTargeting cardiac fibrosis with engineered T cells
Aghajanian, H., Kimura, T., Rurik, J. G., Hancock, A. S., Leibowitz, M. S., Li, L., Scholler, J., Monslow, J., Lo, A., Han, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1546-z · Cited by 801 · cited 3×
“Recently, 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].”
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“Senescent cardiovascular cells specifically contributes to chronic CVD, including atherosclerosis [47], abdominal aortic aneurysm (AAA) [48], thoracic aortic aneurysm (TAA) [49], artery stiffness [50] and heart failure [51].”
BackgroundCD47-blocking antibodies restore phagocytosis and prevent atherosclerosis
Kojima, Y., Volkmer, J.-P., McKenna, K., Civelek, M., Lusis, A. J., Miller, C. L., Direnzo, D., Nanda, V., Ye, J., Connolly, A. J., et al. (2016) · Nature · doi:10.1038/nature18935 · Cited by 683 · cited 1×
“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].”
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DNA Methylation Clocks in Aging: Categories, Causes, and Consequences
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“cytotoxicity [40]; (4) the epigenetic clock based on the DNA methylation profile, which is likely related to biological age other than chronological age [44]; (5) the glomerular filtration rate, which correlates inversely with age [38]; (6) other biological molecules, such as PDGF-BB and VEGF-D, which are positively r…”
BackgroundMatthews, C., Gorenne, I., Scott, S., Figg, N., Kirkpatrick, P., Ritchie, A., Goddard, M., & Bennett, M. (2006) · Circulation Research · doi:10.1161/01.res.0000233315.38086.bc · Cited by 615 · cited 1×
“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…”
BackgroundRadaeva, S., Sun, R., Jaruga, B., Nguyen, V. T., Tian, Z., & Gao, B. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.10.055 · Cited by 610 · cited 1×
“Furthermore, NK cell activation by polyinosinic-polycytidylic acid [152] decreases the senescent cell number in the liver in vivo, leading to reduced liver fibrosis [20].”
BackgroundSecretion of vascular endothelial growth factor by primary human fibroblasts at senescence
Coppé, J.-P., Kauser, K., Campisi, J., & Beauséjour, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603307200 · Cited by 604 · cited 1×
“Senescent cells usually secrete several pro-inflammatory cytokines (such as interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor [TNF]α and monocyte chemo-attractant proteins), growth factors (including platelet-derived growth factor AA [PDGF-AA] [9], vascular endothelial growth factor [VEGF] [33] and insulin-like gr…”
BackgroundTargeting senescent cells enhances adipogenesis and metabolic function in old age
Xu, M., Palmer, A. K., Ding, H., Weivoda, M. M., Pirtskhalava, T., White, T. A., Sepe, A., Johnson, K. O., Stout, M. B., Giorgadze, N., et al. (2015) · eLife · doi:10.7554/elife.12997 · Cited by 604 · cited 1×
“Fat progenitor cells Lipodystrophy and fat loss in old mice [76]”
BackgroundImpaired immune surveillance accelerates accumulation of senescent cells and aging
Ovadya, Y., Landsberger, T., Leins, H., Vadai, E., Gal, H., Biran, A., Yosef, R., Sagiv, A., Agrawal, A., Shapira, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07825-3 · Cited by 578 · cited 3×
“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].”
BackgroundSenescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition
Pereira, B. I., Devine, O. P., Vukmanovic-Stejic, M., Chambers, E. S., Subramanian, P., Patel, N., Virasami, A., Sebire, N. J., Kinsler, V., Valdovinos, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10335-5 · Cited by 556
Sex Differences in Blood Pressure Trajectories Over the Life Course
Ji, H., Kim, A., Ebinger, J. E., Niiranen, T. J., Claggett, B. L., Bairey Merz, C. N., & Cheng, S. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2019.5306 · Cited by 556
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Ogrodnik, M., Zhu, Y., Langhi, L. G. P., Tchkonia, T., Krüger, P., Fielder, E., Victorelli, S., Ruswhandi, R. A., Giorgadze, N., Pirtskhalava, T., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.008 · Cited by 536 · cited 2×
“Although senescent cells can be induced to undergo apoptosis by senolytics [45,60,78,81,120], these apoptotic cells must be finally cleared by the immune system.”
BackgroundLength-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532
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“Additionally, senescent astrocytes mediate dopaminergic neurodegeneration related to PD [57].”
BackgroundA Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.005 · Cited by 514 · cited 1×
“In addition, β-hydroxybutyrate (β-HB) may mediate the effect of a ketogenic diet [113,114], intermittent fasting [115] or exercise [116] on healthspan extension or neuroregeneration because of its anti-inflammation [117], inhibition of vascular cell senescence [118] or immune activation by the formation and maintenanc…”
BackgroundCellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives
Baker, D. J., & Petersen, R. C. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95145 · Cited by 514 · 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…”
BackgroundPhagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis
Schrijvers, D. M., De Meyer, G. R. Y., Kockx, M. M., Herman, A. G., & Martinet, W. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000166517.18801.a7 · Cited by 509
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · cited 2×
“Senescent cells recruit and make immune cells senescent and dysfunctional via SASP, leading to persistent and excessive accumulation of senescent cells [122].”
BackgroundImpairment of an endothelial NAD(+)-H2S signaling network is a reversible cause of vascular aging
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L.-J., Osborne, B., Joshi, S., Lu, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.02.008 · Cited by 496
TORC1 inhibition enhances immune function and reduces infections in the elderly
Mannick, J. B., Morris, M., Hockey, H.-U. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1564 · Cited by 496 · cited 1×
“A phase 2a clinical study with a low-dose combination of a catalytic (BEZ235) plus an allosteric (RAD001) mTOR inhibitor that selectively inhibits mTOR downstream target of rapamycin complex 1 (TORC1) for 6 weeks demonstrates that mTOR inhibitor therapy is safe, enhances immune function, decreases the incidence of upp…”
BackgroundKetogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., & Verdin, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.004 · Cited by 493 · cited 1×
“In addition, β-hydroxybutyrate (β-HB) may mediate the effect of a ketogenic diet [113,114], intermittent fasting [115] or exercise [116] on healthspan extension or neuroregeneration because of its anti-inflammation [117], inhibition of vascular cell senescence [118] or immune activation by the formation and maintenanc…”
BackgroundAcceleration of β Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes
Aguayo-Mazzucato, C., Andle, J., Lee, T. B., Midha, A., Talemal, L., Chipashvili, V., Hollister-Lock, J., van Deursen, J., Weir, G., & Bonner-Weir, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.006 · Cited by 469
NF-κB inhibition delays DNA damage–induced senescence and aging in mice
Tilstra, J. S., Robinson, A. R., Wang, J., Gregg, S. Q., Clauson, C. L., Reay, D. P., Nasto, L. A., St Croix, C. M., Usas, A., Vo, N., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45785 · Cited by 462 · cited 1×
“extrinsic factors, including telomere (the repetitive sequences of DNA at the end of eukaryotic chromosomes) attrition [16], DNA damage [22,23], accumulated cytosolic DNA from the nucleus, mitochondrial and fragmented chromatin, oncogenes such as RAS and RAF [24], mitochondrial dysfunction [25] and reactive oxygen or…”
BackgroundSoriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., Di Gialleonardo, V., Cippitelli, M., Fionda, C., Petrucci, M. T., Guarini, A., et al. (2009) · Blood · doi:10.1182/blood-2008-08-173914 · Cited by 460 · cited 2×
“These ligands enhance NK cell susceptibility [137].”
BackgroundAgeing, Cellular Senescence and Neurodegenerative Disease
Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102937 · Cited by 448 · cited 1×
“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).”
BackgroundRegulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution
Proto, J. D., Doran, A. C., Gusarova, G., Yurdagul, A., Sozen, E., Subramanian, M., Islam, M. N., Rymond, C. C., Du, J., Hook, J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.015 · Cited by 441
Iannello, A., Thompson, T. W., Ardolino, M., Lowe, S. W., & Raulet, D. H. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130783 · Cited by 414 · cited 1×
“However, 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].”
BackgroundPersonal aging markers and ageotypes revealed by deep longitudinal profiling
Ahadi, S., Zhou, W., Schüssler-Fiorenza Rose, S. M., Sailani, M. R., Contrepois, K., Avina, M., Ashland, M., Brunet, A., & Snyder, M. (2020) · Nature Medicine · doi:10.1038/s41591-019-0719-5 · Cited by 408 · cited 5×
“All the results suggest that different individuals have distinct ageotypes [38].”
BackgroundInfluentialSelective Persulfide Detection Reveals Evolutionarily Conserved Antiaging Effects of S-Sulfhydration
Živanović, J., Kouroussis, E., Kohl, J. B., Adhikari, B., Bursać, B. N., Schott-Roux, S., Petrovic, D., Miljković, J. L., Thomas‐López, D., Jung, Y., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.10.007 · Cited by 401 · cited 1×
“H2S plays this role via the regulation of endothelial NAD+ levels [42] or post-translational modification of reactive cysteine residues by protein persulfidation (S-sulfhydration) [97].”
BackgroundSkp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence
Lin, H.-K., Chen, Z., Wang, G., Nardella, C., Lee, S.-W., Chan, C.-H., Yang, W.-L., Wang, J., Egia, A., Nakayama, K. I., et al. (2010) · Nature · doi:10.1038/nature08815 · Cited by 400 · cited 1×
“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].”
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Chimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., Di Meglio, F., Nadal-Ginard, B., Frustaci, A., Leri, A., et al. (2003) · Circulation Research · doi:10.1161/01.res.0000093985.76901.af · Cited by 386
Identification and characterization of Cardiac Glycosides as senolytic compounds
Triana-Martínez, F., Picallos-Rabina, P., Da Silva-Álvarez, S., Pietrocola, F., Llanos, S., Rodilla, V., Soprano, E., Pedrosa, P., Ferreirós, A., Barradas, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12888-x · Cited by 384 · cited 1×
“Although senescent cells can be induced to undergo apoptosis by senolytics [45,60,78,81,120], these apoptotic cells must be finally cleared by the immune system.”
BackgroundThe roles of senescence and telomere shortening in cardiovascular disease
Fyhrquist, F., Saijonmaa, O. J., & Strandberg, T. E. (2013) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2013.30 · Cited by 373 · cited 2×
“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…”
BackgroundCircadian Rhythms, Sleep, and Disorders of Aging
Mattis, J., & Sehgal, A. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.02.003 · Cited by 369 · cited 1×
“One of the two most common measurements is Fried’s frailty phenotype (known as the Cardiovascular Health Study [CHS] Index), which includes weight loss, weakness (lower grip strength [40]), slow gait speed, low physical activity (voluntary exercise for moue) and decreased exercise endurance [42]; (2) disordered circad…”
BackgroundMitochondrial fission promotes the continued clearance of apoptotic cells by macrophages
Wang, Y., Subramanian, M., Yurdagul, A., Barbosa-Lorenzi, V. C., Cai, B., de Juan-Sanz, J., Ryan, T. A., Nomura, M., Maxfield, F. R., & Tabas, I. (2017) · Cell · doi:10.1016/j.cell.2017.08.041 · Cited by 364
Senescent cells and osteoarthritis: a painful connection
Jeon, O. H., David, N. E., Campisi, J., & Elisseeff, J. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95147 · Cited by 359 · 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…”
BackgroundThorp, E., Cui, D., Schrijvers, D. M., Kuriakose, G., & Tabas, I. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.167197 · Cited by 357
Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes
Thompson, P. J., Shah, A., Ntranos, V., Van Gool, F., Atkinson, M., & Bhushan, A. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.021 · Cited by 353 · cited 1×
“Beta cells Type 1 diabetes and type 2 diabetes [64,65]”
Backgroundp16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., et al. (2016) · Nature Medicine · doi:10.1038/nm.4054 · Cited by 351
Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability
Wang, J., Uryga, A. K., Reinhold, J., Figg, N., Baker, L., Finigan, A., Gray, K., Kumar, S., Clarke, M., & Bennett, M. (2015) · Circulation · doi:10.1161/circulationaha.115.016457 · Cited by 349
NKG2D ligands mediate immunosurveillance of senescent cells
Sagiv, A., Burton, D. G. A., Moshayev, Z., Vadai, E., Wensveen, F., Ben-Dor, S., Golani, O., Polic, B., & Krizhanovsky, V. (2016) · Aging · doi:10.18632/aging.100897 · Cited by 345 · cited 2×
“This selectivity is due to selective upregulation of NKG2D ligands MICA and ULBP2 in senescent IMR-90 cells but not growing or quiescent cells [151].”
BackgroundBlocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells
Kamiya, T., Seow, S. V., Wong, D., Robinson, M., & Campana, D. (2019) · Journal of Clinical Investigation · doi:10.1172/jci123955 · Cited by 345 · cited 1×
“Collectively, agents blocking the interaction between HLAE and NKG2A [124], the humanized anti-NKG2A monoclonal antibody monalizumab [154] and NKG2A protein expression blockers [155] would be promising strategies for the immune clearance of senescent cells and subsequent anti-ageing and chronic diseases.”
BackgroundSingle-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
Hashimoto, K., Kouno, T., Ikawa, T., Hayatsu, N., Miyajima, Y., Yabukami, H., Terooatea, T., Sasaki, T., Suzuki, T., Valentine, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907883116 · Cited by 343 · cited 1×
“However, the supercentenarians have a dramatic reduction of the B-cell number compared with controls [127].”
BackgroundBaumeister, S. H. C., Murad, J., Werner, L. L., Daley, H., Trebeden‐Negre, H., Gicobi, J. K., Schmucker, A. C., Reder, J., Sentman, C. L., Gilham, D. E., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0307 · Cited by 334 · cited 1×
“Therefore, it may be possible to target senescent cells by engineering T cells expressing NKG2D-CAR (NKG2D-CAR-T cells) that recognize NKG2D ligands on the surface of senescent cells based on cancer research [159].”
BackgroundClearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium
Brighton, P. J., Maruyama, Y., Fishwick, K., Vrljicak, P., Tewary, S., Fujihara, R., Muter, J., Lucas, E. S., Yamada, T., Woods, L., et al. (2017) · eLife · doi:10.7554/elife.31274 · Cited by 323 · cited 1×
“Immune Cells Eliminated Senescent Cells Outcomes In Vivo References CAR-T cells Fibroblasts Fibrosis reduction in mouse heart [134] CD4+ T cells Murine hepatocytes Suppression of mouse liver cancer [130] CD8+ T cells Fibroblasts N/A [124] Macrophages Uterine senescent cells Maintain postpartum uterine function in mous…”
BackgroundAged-senescent cells contribute to impaired heart regeneration
Lewis‐McDougall, F. C., Ruchaya, P. J., Domenjo‐Vila, E., Shin Teoh, T., Prata, L., Cottle, B. J., Clark, J. E., Punjabi, P. P., Awad, W., Torella, D., et al. (2019) · Aging Cell · doi:10.1111/acel.12931 · Cited by 317 · cited 1×
“Cardiac progenitor cells Impaired heart regeneration [66]”
Late-life rapamycin treatment reverses age-related heart dysfunction
Flynn, J. M., O’Leary, M. N., Zambataro, C. A., Academia, E. C., Presley, M. P., Garrett, B., Zykovich, A., Mooney, S. D., Strong, R., Rosen, C. J., et al. (2013) · Aging Cell · doi:10.1111/acel.12109 · Cited by 314 · cited 1×
“Rapamycin treatment also results in beneficial behavioral, skeletal and motor changes in old mice [100].”
BackgroundWeiskopf, D., Bangs, D. J., Sidney, J., Kolla, R. V., Silva, A. D. D., de Silva, A. M., Crotty, S., Peters, B., & Sette, A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505956112 · Cited by 312
Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis
Yurdagul, A., Doran, A. C., Cai, B., Fredman, G., & Tabas, I. A. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00086 · Cited by 300
The role of efferocytosis in atherosclerosis
Kojima, Y., Weissman, I. L., & Leeper, N. J. (2017) · Circulation · doi:10.1161/circulationaha.116.025684 · Cited by 289
Small nucleoli are a cellular hallmark of longevity
Tiku, V., Jain, C., Raz, Y., Nakamura, S., Heestand, B., Liu, W., Späth, M., Suchiman, H. E. D., Müller, R.-U., Slagboom, P. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms16083 · Cited by 287 · cited 1×
“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…”
BackgroundHost-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy
Pryor, R., Norvaisas, P., Marinos, G., Best, L., Thingholm, L. B., Quintaneiro, L. M., De Haes, W., Esser, D., Waschina, S., Lujan, C., et al. (2019) · Cell · doi:10.1016/j.cell.2019.08.003 · Cited by 274 · cited 1×
“a mediator of metformin effects on host fatty acid metabolism and lifespan extension [109].”
BackgroundMetformin as Anti-Aging Therapy: Is It for Everyone?
Soukas, A. A., Hao, H., & Wu, L. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.015 · Cited by 266 · cited 1×
“Given the uncertain side effects (vitamin B12 deficiency, lactic acidosis and gastrointestinal side effects) of metformin presenting in some individuals [104], personal metformin therapy for anti-ageing may demand more in-depth study.”
BackgroundChen, H.-Z., Wang, F., Gao, P., Pei, J.-F., Liu, Y., Xu, T.-T., Tang, X., Fu, W.-Y., Lu, J., Yan, Y.-F., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.308895 · Cited by 265 · cited 1×
“Senescent cardiovascular cells specifically contributes to chronic CVD, including atherosclerosis [47], abdominal aortic aneurysm (AAA) [48], thoracic aortic aneurysm (TAA) [49], artery stiffness [50] and heart failure [51].”
BackgroundSelf-citationRosenkranz, D., Weyer, S. W., Tolosa, E., Gaenslen, A., Berg, D., Leyhe, T., Gasser, T., & Stoltze, L. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.05.011 · Cited by 264 · cited 1×
“It was reported that aged mice [125] and humans [125,126] have an increased proportion and suppressive activity of FOXP3+ regulatory T (Tregs) cells, which suppress T effector cell function.”
BackgroundNucleolar expansion and elevated protein translation in premature aging
Buchwalter, A., & Hetzer, M. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00322-z · Cited by 263 · cited 1×
“Senescent cells generally demonstrate an enlarged and flattened cell morphology [27] and expanded nucleoli [28,29], enhanced senescence-associated betagalactosidase (SA-β-gal) activity [30], telomere shortening, elevation of the cyclin-dependent kinase inhibitor p16 [11,31] or p21 [32], macromolecular damage and metab…”
BackgroundTissue-resident macrophages are locally programmed for silent clearance of apoptotic cells
Roberts, A. W., Lee, B. L., Deguine, J., John, S., Shlomchik, M. J., & Barton, G. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.10.006 · Cited by 261 · cited 2×
“Specific populations of innate immune effector macrophages take up apoptotic cells in particular tissues, known as efferocytosis, which prevents apoptotic cells from being necrotic or proinflammatory [138].”
BackgroundRobust, universal biomarker assay to detect senescent cells in biological specimens
Evangelou, K., Lougiakis, N., Rizou, S. V., Kotsinas, A., Kletsas, D., Muñoz‐Espín, D., Kastrinakis, N. G., Pouli, N., Marakos, P., Townsend, P., et al. (2017) · Aging Cell · doi:10.1111/acel.12545 · Cited by 259 · cited 1×
“It can be visualized in lysosomes by light microscopy or a specific histochemical stain with a biotin-linked Sudan Black B (SBB) analog [37].”
BackgroundSenescent human melanocytes drive skin ageing via paracrine telomere dysfunction
Victorelli, S., Lagnado, A., Halim, J., Moore, W., Talbot, D., Barrett, K., Chapman, J., Birch, J., Ogrodnik, M., Meves, A., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2019101982 · Cited by 258 · cited 1×
“Glial cells Neuropsychiatric disorders, including anxiety and depression [81] Hematopoietic stem cells Immune function decline [82] Hepatic stellate cells Liver fibrosis [20,83] Hepatocytes Age-related hepatic steatosis [84] Macrophages Atherosclerosis [47] Melanocytes Human skin ageing [85] Muscle stem cells Sarcopen…”
BackgroundPhysiological and pathological consequences of cellular senescence
Burton, D. G. A., & Krizhanovsky, V. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1691-3 · Cited by 253 · cited 2×
“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].”
BackgroundWalaszczyk, A., Dookun, E., Redgrave, R., Tual‐Chalot, S., Victorelli, S., Spyridopoulos, I., Owens, A., Arthur, H. M., Passos, J. F., & Richardson, G. D. (2019) · Aging Cell · doi:10.1111/acel.12945 · Cited by 250
Hoenicke, L., & Zender, L. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs124 · Cited by 248
Essential role for premature senescence of myofibroblasts in myocardial fibrosis
Meyer, K., Hodwin, B., Ramanujam, D., Engelhardt, S., & Sarikas, A. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.02.047 · Cited by 247 · cited 1×
“Myofibroblasts Myocardial fibrosis reduction [86]”
Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases
Song, P., Ramprasath, T., Wang, H., & Zou, M. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2504-2 · Cited by 247 · cited 1×
“NAD+ is usually generated by the kynurenine pathway of tryptophan catabolism [92] and salvage pathway [93].”
BackgroundSelf-citationGranule exocytosis mediates immune surveillance of senescent cells
Sagiv, A., Biran, A., Yon, M., Simon, J., Lowe, S. W., & Krizhanovsky, V (2013) · Oncogene · doi:10.1038/onc.2012.206 · Cited by 240 · cited 1×
“Thus, mice with defects in granule exocytosis accumulate senescent stellate cells and display stronger liver fibrosis in response to a fibrogenic agent [131].”
BackgroundDifferent tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs
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“Senescent cells usually secrete several pro-inflammatory cytokines (such as interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor [TNF]α and monocyte chemo-attractant proteins), growth factors (including platelet-derived growth factor AA [PDGF-AA] [9], vascular endothelial growth factor [VEGF] [33] and insulin-like gr…”
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Strategies targeting cellular senescence
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“Generally, senescent cells can be removed by apoptosis and the immune system [121,122].”
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“The results indicate that metformin modulates metabolic and nonmetabolic gene expression in skeletal muscle and subcutaneous adipose tissues of older persons [110].”
BackgroundCardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence
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Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis
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β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4
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Cellular senescence links aging and diabetes in cardiovascular disease
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“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…”
BackgroundJustice, J. N., Gregory, H., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., Kritchevsky, S. B., & Nicklas, B. J. (2018) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glx134 · Cited by 129
Replicatively senescent cells are arrested in G1 and G2 phases
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“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].”
BackgroundSeneviratne, A. N., Edsfeldt, A., Cole, J. E., Kassiteridi, C., Swart, M., Park, I., Green, P., Khoyratty, T., Saliba, D., Goddard, M. E., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.027844 · Cited by 117 · cited 1×
“For example, interferon regulatory factor 5 (IRF5) transcription factor enhances vulnerable plaque formation in hyperlipidemic apolipoprotein E-deficient (ApoE-/-) mice through the induction of pro-inflammatory CD11c+ macrophages within atherosclerotic lesions and increasing the expansion of the necrotic core by inhib…”
BackgroundYun, T. J., Lee, J. S., Machmach, K., Shim, D., Choi, J., Wi, Y. J., Jang, H. S., Jung, I.-H., Kim, K., Yoon, W. K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.04.010 · Cited by 116 · cited 1×
“Indoleamine 2,3dioxygenase 1 (IDO1)-expressing and chemokine (C-C motif) receptor 9 (CCR9)-positive plasmacytoid dendritic cells (pDCs) in the aorta locally induce aortic Treg cells, which produce IL-10 and subsequently prevent atherogenesis in mice [163].”
BackgroundMorgan, R. G., Ives, S. J., Lesniewski, L. A., Cawthon, R. M., Andtbacka, R. H. I., Noyes, R. D., Richardson, R. S., & Donato, A. J. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00197.2013 · Cited by 115 · cited 1×
“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…”
BackgroundDecrease and Senescence of Endothelial Progenitor Cells in Patients with Preeclampsia
Sugawara, J., Mitsui‐Saito, M., Hayashi, C., Hoshiai, T., Senoo, M., Chisaka, H., Yaegashi, N., & Okamura, K. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0532 · Cited by 110
Rapamycin directly activates lysosomal mucolipin TRP channels independent of mTOR
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“Recently, rapamycin was reported to exert in vivo neuroprotective and anti-ageing effects via the activation of lysosomal mucolipin TRP channels, independent of mTOR [98].”
BackgroundA GPR174–CCL21 module imparts sexual dimorphism to humoral immunity
Zhao, R., Chen, X., Ma, W., Zhang, J., Guo, J., Zhong, X., Yao, J., Sun, J., Rubinfien, J., Zhou, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1873-0 · Cited by 104 · cited 1×
“Males generally have a shorter average lifespan than females partly due to fewer B cells and weaker B-cell-mediated humoral immunity inhibited by the CCL21-GPR174-Gαi pathway [123].”
BackgroundT-cell senescence contributes to abnormal glucose homeostasis in humans and mice
Yi, H., Kim, S. Y., Kim, J. T., Lee, Y., Moon, J. S., Kim, M., Kang, Y. E., Joung, K. H., Lee, J. H., Kim, H. J., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1494-4 · Cited by 102 · cited 1×
“T cells Abnormal glucose homeostasis, insulin resistance, physical frailty [46,89]”
BackgroundEndothelial cell senescence and thrombosis: Ageing clots
Bochenek, M. L., Schütz, E., & Schäfer, K. (2016) · Thrombosis Research · doi:10.1016/j.thromres.2016.09.019 · Cited by 96 · cited 1×
“Accumulation of senescent endothelial cells leads to cardiovascular thrombotic complications, including arterial (acute myocardial infarction, stroke) and venous (deep vein thrombosis, pulmonary embolism) thrombotic events [52].”
BackgroundF4/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus
Egashira, M., Hirota, Y., Shimizu-Hirota, R., Saito-Fujita, T., Haraguchi, H., Matsumoto, L., Matsuo, M., Hiraoka, T., Tanaka, T., Akaeda, S., et al. (2017) · Endocrinology · doi:10.1210/en.2016-1886 · Cited by 90 · cited 2×
“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].”
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“It was reported that mitochondria-targeted gasotransmitter hydrogen sulfide (H2S) delays endothelium senescence [96].”
BackgroundSenescent endothelial cells: Potential modulators of immunosenescence and ageing
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“Senescent endothelial cells potentially modulate immunosenescence [53].”
Vázquez-Padrón, R. I., Lasko, D. S., Li, S., Louis, L. B., Pestana, I. A., Pang, M., Liotta, C., Fornoni, A., Aı̈touche, A., & Pham, S. M. (2004) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2004.08.034 · Cited by 79
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“Senescent cardiovascular cells specifically contributes to chronic CVD, including atherosclerosis [47], abdominal aortic aneurysm (AAA) [48], thoracic aortic aneurysm (TAA) [49], artery stiffness [50] and heart failure [51].”
BackgroundLefranc, C., Friederich‐Persson, M., Braud, L., Palacios, R., Karlsson, S., Boujardine, N., Motterlini, R., Jaisser, F., & Cat, A. N. D. (2019) · Hypertension · doi:10.1161/hypertensionaha.118.11873 · Cited by 72
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“Cellular senescence traditionally impairs stem-cell function (also termed as stemness) [58].”
BackgroundNg, T. P., Camous, X., Nyunt, M. S. Z., Vasudev, A., Tan, C. T. Y., Feng, L., Fulop, T., Yap, K. B., & Larbi, A. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.5 · Cited by 58 · cited 2×
“T cells Abnormal glucose homeostasis, insulin resistance, physical frailty [46,89]”
BackgroundEspinoza, S. E., Musi, N., Wang, C.-P., Michalek, J. E., Orsak, B., Romo, T. Q., Powers, B., Conde, A., Moris, M., Bair‐Kelps, D., et al. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz078 · Cited by 52 · cited 1×
“The phase 2 clinical trial (NCT02570672) “Metformin for Preventing Frailty in High-risk Older Adults,” which considered frailty as a vital endpoint, was undertaken since 2015 [111].”
BackgroundSessions, G. A., Copp, M. E., Liu, J., Sinkler, M. A., D’Costa, S., & Diekman, B. O. (2019) · The FASEB Journal · doi:10.1096/fj.201900815rr · Cited by 52 · cited 1×
“Astrocytes Neuropathology related to Parkinson’s disease [57] Astrocytes and microglia Cognitive decline [18] Beige progenitor cells Age-related decline in beiging and thermogenesis [63] Beta cells Type 1 diabetes and type 2 diabetes [64,65] Cardiac progenitor cells Impaired heart regeneration [66] Cardiac fibroblasts…”
BackgroundYang, Z., Li, Q., Wang, X., Jiang, X., Zhao, D., Lin, X., He, F., & Tang, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804094115 · Cited by 46 · cited 1×
“reported that the C-type lectin receptor LSECtin (Clec4g) on colon macrophages is required for macrophage engulfment and clearance of apoptotic cells, contributing to intestinal repair in dextran sulphate sodium-induced colitis [146].”
BackgroundGeneration of senescent cell antigen on old cells initiates IgG binding to a neoantigen.
Kay, M. M. B. (1993) · PubMed · Cited by 44
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“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…”
BackgroundTaming expectations of metformin as a treatment to extend healthspan
Konopka, A. R., & Miller, B. F. (2019) · GeroScience · doi:10.1007/s11357-019-00057-3 · Cited by 42 · cited 1×
“The recent multicenter trial “Targeting Ageing with Metformin (TAME)” focusing on targeting ageing and chronic conditions may be supported by NIH in the future [112].”
BackgroundProfessor Toshio Ito: A clairvoyant in pericyte biology.
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“Hepatic stellate cells Liver fibrosis [20,83]”
Absence of AMPKα2 accelerates cellular senescence via p16 induction in mouse embryonic fibroblasts
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Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
“(CAR-)T/NK for eliminating senescent cells 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) It was found that anti-uPAR-CAR-T cells were effective in removing senescent cells in vitro and precancerous and maligna…”
BackgroundImmunosenescence and inflammaging in the aging process: age-related diseases or longevity?
Santoro, A., Bientinesi, E., & Monti, D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101422 · Cited by 603
Personal aging markers and ageotypes revealed by deep longitudinal profiling
Ahadi, S., Zhou, W., Schüssler-Fiorenza Rose, S. M., Sailani, M. R., Contrepois, K., Avina, M., Ashland, M., Brunet, A., & Snyder, M. (2020) · Nature Medicine · doi:10.1038/s41591-019-0719-5 · Cited by 408
Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Marín, I., Boix, O., García-Garijo, A., Sirois, I., Caballé, A., Zarzuela, E., Ruano, I., Attolini, C. S., Prats, N., Lopez-Dominguez, J. A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0523 · Cited by 365
“The immune clearance of senescent cells is mediated by different populations of leukocytes, being better studied those belonging to the innate immune system (5, 16, 17).”
BackgroundSenescence mechanisms and targets in the heart
Chen, M. S., Lee, R. T., & Garbern, J. C. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab161 · Cited by 353
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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