Senescence of activated stellate cells limits liver fibrosis
Open accessAbstract
Summary Cellular senescence acts as a potent mechanism of tumor suppression; however, its functional contribution to non-cancer pathologies has not been examined. Here we show that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis. The senescent cells are derived primarily from activated hepatic stellate cells, which initially proliferate in response to liver damage and produce the extracellular matrix deposited in the fibrotic scar. In mice lacking key senescence regulators, stellate cells continue to proliferate, leading to excessive liver fibrosis. Furthermore, senescent activated stellate cells exhibit gene expression profile consistent with cell cycle exit, reduced secretion of extracellular matrix components, enhanced secretion of extracellular matrix degrading enzymes, and enhanced immune surveillance. Accordingly natural killer cells preferentially kill senescent activated stellate cells in vitro and in vivo, thereby facilitating the resolution of fibrosis. Therefore, the senescence program limits the fibrogenic response to acute tissue damage.
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There are theoretical side effects of eliminating senescent cells, including impaired wound healing or fibrosis during liver regeneration.
“There are a number of theoretical side effects of eliminating senescent cells, including impaired wound healing or fibrosis during liver regeneration (Krizhanovsky et al., 2008; Demaria et al., 2014).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Krizhanovsky et al., 2008
The Discussion (page unavailable) says senescence of activated stellate cells limits fibrosis, but distinguishes that protective process from clearing cells after they become senescent. Rather than identifying fibrosis as a risk of eliminating senescent cells, it says their immune clearance helps resolve fibrosis and proposes enhancing clearance as a potential treatment. The paper does not assess impaired wound healing during liver regeneration. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAmong the cells that participate in clearance of senescent cells are natural killer cells, macrophages, and T cells.
“Among the cells that participate in the clearance of senescent cells are natural killer cells, macrophages, and T cells (131, 135, 139).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [139]
The Discussion says natural killer (NK) cells clear senescent activated stellate cells, and the Results show that altering NK-cell activity affects their clearance. The Results also place macrophages near cells with senescence markers and mention T cells as potential participants in NK-influenced killing, but do not establish that macrophages or T cells participate in clearing the senescent cells studied here. The indexed passages provide section labels but no page numbers. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn a mouse model of acute liver injury, the injury induced senescence of hepatic stellate cells, which were eventually cleared by the immune system, principally by natural killer cells.
“In a mouse model of acute liver injury, the injury induced the senescence of hepatic stellate cells, which were eventually cleared by the immune system (principally by natural killer cells) (139).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [139]
The Results section reports that senescent activated hepatic stellate cells were cleared from mouse livers, principally through natural killer cell activity. But the Introduction and Experimental Procedures describe repeated CCl4 treatment to induce fibrosis—a model of chronic liver damage, not a model of acute liver injury. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredWhen acute liver injury was performed on mice deficient in the p53/p21 and p16INK4a/pRB pathways-mice deficient in undergoing a senescence response-healing was accompanied by a marked increase in fibrosis.
“When the injury was performed on mice that were deficient in the p53/p21 and p16INK4a/pRB pathways—that is, mice deficient in undergoing a senescence response—healing was accompanied by a marked increase in fibrosis (139).”
From Aging, Cellular Senescence, and Cancer (2013) · cites this paper as [139]
The Results section (“Fibrosis progression is restricted by an intact senescence machinery”; page unavailable) reports that mice lacking both p53 and INK4a/ARF had impaired senescence and more than 50% greater fibrotic area than wild-type mice. But the experiment used repeated CCl4 treatment, which the paper describes as chronic liver damage, not acute injury. The Results section on fibrosis reversion also reports more lesions remaining in the double mutants after treatment stopped, rather than an increase arising during healing from an acute injury. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSASP from these cells attracts NK cells that remove senescent cells from the liver and restore liver homeostasis.
“SASP from these cells attracts natural killer (NK) cells that eliminate senescent cells from the liver to restore liver homeostasis145.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results report that senescent stellate cells upregulate secretory and immune-surveillance genes, and that NK-cell activity promotes their clearance and fibrosis resolution in mice. But the Results describe signals from senescent cells attracting immune cells as a possibility, not an established SASP-driven recruitment mechanism; the Discussion likewise proposes, rather than demonstrates, a return to the liver’s pre-damaged state. Page numbers are unavailable in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Cellular senescence helps maintain tissue structure and function after injury.
“Cellular senescence contributes to the maintenance of the structure and the function of tissues following injury.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Discussion reports that senescence of activated hepatic stellate cells limits fibrosis after liver damage and describes it as a homeostatic mechanism that helps tissue return to its pre-damaged state. It says this mechanism may apply to other wound-healing responses, but does not establish maintenance of tissue structure and function after injury generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe homeostatic role of senescent cells depends on their removal by the immune system after their beneficial functions are completed.
“The homeostatic function of senescent cells is dependent on their elimination by the immune system, once their beneficial functions have been performed145,151.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results section reports that reducing NK-cell activity left more senescent stellate cells and more fibrosis, supporting immune clearance as a contributor to fibrosis resolution. The Discussion describes this as a homeostatic mechanism but cautions that not all senescent cells are immune targets. The paper does not establish that homeostatic function generally depends on clearance, or that clearance occurs only after beneficial functions are complete. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSenescence immunosurveillance is essential to limit pathological fibrotic conditions and ageing.
“Senescence immunosurveillance is also essential to limit pathological fibrotic conditions and ageing20,145,151,157.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results section ('Senescent stellate cells are selectively targeted by NK cells'; page unavailable) reports that inhibiting NK-cell activity delayed clearance of senescent cells and left significantly more liver fibrosis, supporting a role for immune surveillance in limiting fibrosis. The Discussion (page unavailable) only speculates that declining immune function may contribute to senescent-cell accumulation in aged tissues; it does not establish that senescence immunosurveillance is essential to limit ageing or fibrotic conditions generally. (LLM, conf=0.87)
Experimental — accuracy not yet measuredNK cells, T cells and macrophages can physically interact with senescent cells in both pathological and physiological conditions.
“Among these cell types, NK cells, T cells and macrophages can physically interact with senescent cells in pathological and physiological conditions131,132,145,150,153–156.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results section, “Senescent stellate cells are selectively targeted by NK cells” (page unavailable), shows NK cells attacking senescent cells in vitro. The Results section, “Immune cells are found in proximity to senescent cells in fibrotic livers” (page unavailable), reports macrophages and activated lymphocytes near senescent-marker-positive cells in diseased mice, but does not identify those lymphocytes as T cells or establish physical contact by T cells or macrophages. It does not demonstrate these interactions under physiological conditions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredActivating the innate immune response with poly(I:C), which mimics viral infection, enhances clearance of senescent cells.
“Stimulation of innate immune response with poly(I:C), a simulator of viral infection, improves senescent cell clearance145.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results section, “Senescent stellate cells are selectively targeted by NK cells” (page unavailable), says polyI:C was used to enhance the immune response and that treated mouse livers contained fewer senescent cells than controls. Our copy does not describe polyI:C as simulating viral infection, so that characterization is not supported by this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSenescent cells are surveilled by several innate and adaptive immune cell types, including NK cells, T cells, and macrophages.
“Senescent cells are indeed subjected to immunosurveillance by multiple components of innate and adaptive immunity, including NK cells, T cells and macrophages145,151,153–156.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
The Results section, “Senescent stellate cells are selectively targeted by NK cells” (page unavailable), demonstrates NK-cell killing of senescent cells. “Immune cells are found in proximity to senescent cells in fibrotic livers” reports macrophages and activated lymphocytes nearby, but does not establish that macrophages or T cells surveil senescent cells. The paper therefore supports NK-cell surveillance, not the full list attributed to it. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMouse hepatic stellate cells exhibit SA-β-gal activity and expression of Cdkn1a, Cdkn2a and SASP components in models of liver injury.
“Mouse hepatic stellate cells have also been shown to exhibit senescence-associated markers such as SA-β-gal activity and expression of Cdkn1a, Cdkn2a and SASP components in models of liver injury163,164.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [163]
The Results section, “Senescent activated stellate cells accumulate in the cirrhotic liver,” reports that most SA-β-gal-positive cells in mouse fibrotic liver also expressed the stellate-cell marker αSMA. It reports p21 and p16 in injured mouse livers, but demonstrates their co-localization with αSMA in human liver sections. The Results section on immune modulators describes SASP-related gene expression in cultured human, not mouse, stellate cells; thus the full set of markers is not established for mouse stellate cells in liver-injury models. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCellular senescence has beneficial roles in tissue remodelling during embryogenesis and wound healing.
“Cellular senescence, a stress-induced irreversible growth arrest often characterized by p16 Ink4a expression and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing.”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [7]
The Discussion (page not provided) reports that senescence of activated hepatic stellate cells limits fibrosis during a wound-healing response and helps damaged liver tissue return toward its prior state. It suggests this mechanism may apply to other wound-healing responses, but our copy does not address tissue remodelling during embryogenesis. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn response to liver injury, hepatic stellate cells proliferate and produce extracellular matrixes for tissue repair before undergoing cellular senescence to prevent fibrosis.
“In response to liver injury, hepatic stellate cells (HSC) began to proliferate and produce extracellular matrixes for tissue repair before undergoing cellular senescence to prevent fibrosis.38, 39”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [39]
The Introduction and Discussion say that activated HSCs proliferate after liver damage, produce extracellular matrix, and subsequently senesce. The Discussion says senescence limits excessive fibrosis and aids its resolution, not that it prevents fibrosis altogether; fibrosis can still advance during chronic injury. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSimilar antifibrotic effects of senescent cells have been observed in the kidneys, liver and lungs in mouse models.
“similar antifibrotic effects of senescent cells have been observed in the kidneys, liver and lungs in mouse models 10-12”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [10]
The Introduction and Results (‘Cellular senescence facilitates the reversion of fibrosis’; page numbers not provided) show that senescence limits liver fibrosis in mice. This source does not establish the claimed antifibrotic effects in kidneys or lungs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSenescent cells express surface-bound ligands and adhesion molecules that target them for attack by natural killer and other immune cells.
“Senescent cells express surface-bound ligands and adhesion molecules that target them for attack by natural killer and other immune cells (Krizhanovsky et al., 2008)”
From Four faces of cellular senescence (2011) · cites this paper as Krizhanovsky et al., 2008
The Results report that senescent activated stellate cells and IMR-90 cells upregulate NK-cell ligands and the adhesion molecule CD58, and are preferentially killed by NK cells. The Discussion says other immune components contribute, but cautions that not all senescent cells may be immune targets. The claim overgeneralizes these findings to senescent cells without qualification. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSenescent stromal cells help resolve excessive fibrosis after skin or liver injury.
“Senescent stromal cells were shown to help resolve excessive fibrosis after skin or liver injury (Jun and Lau, 2010; Krizhanovsky et al., 2008).”
From An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA (2014) · cites this paper as Krizhanovsky et al., 2008
Matrix metalloproteinases that comprise the SASP were proposed to facilitate tissue repair by promoting collagen degradation, thereby limiting fibrosis.
“and the matrix metalloproteinases that comprise the SASP (Coppé et al., 2008, 2010b) were proposed to facilitate tissue repair by promoting collagen degradation, thereby limiting fibrosis (Jun and Lau, 2010; Krizhanovsky et al., 2008).”
From An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA (2014) · cites this paper as Krizhanovsky et al., 2008
Experimental — accuracy not yet measuredIn liver fibrosis, senescence restricts proliferation and expansion of ECM-producing activated hepatic stellate cells, limiting progression of the pathology after liver damage.
“in liver fibrosis, a condition associated with scarring of the liver and decrease in its function, senescence limits the proliferation and expansion of ECM-producing activated hepatic stellate cells145,146. This response limits the progression of the pathology following liver damage.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [145]
Senescent cells have beneficial effects in injury repair and tissue remodelling.
“Furthermore, recent studies showing that senescent cells have beneficial effects in injury repair and tissue remodelling 6 - 10 have called into question the simplistic view of senescence as only a driver of age-dependent pathologies, raising the specter that senescent cell clearance might remove useful cells in addition to detrimental ones.”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [7]
Senescent cells have shown beneficial effects as tumour suppressors, during embryo development, and in liver and skin repair or reprogramming.
“By contrast, senescent cells have shown beneficial effects as tumour suppressors, during embryo development, and in liver and skin repair18–21 or reprogramming22–24.”
From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [19]
Senescence may be requisite for optimal cutaneous wound healing and may restrict pathological liver fibrosis.
“Conversely, senescence is autonomously anti-proliferative, may be requisite for optimal cutaneous wound healing9 and may restrict pathological liver fibrosis10.”
From Cellular senescence mediates fibrotic pulmonary disease (2017) · cites this paper as [10]
The SASP can have a major impact on various biological processes, including cell proliferation, angiogenesis, inflammation, epithelial-to-mesenchymal transition, tissue repair and wound healing.
“The SASP can have a major impact on various biological processes, including cell proliferation, angiogenesis, inflammation16, epithelial-to-mesenchymal transition17, tissue repair18 and wound healing3 (Fig. 2).”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [18]
The SASP contributes to the surveillance and elimination of senescent cells by the immune system.
“The SASP also contributes to the surveillance and elimination of senescent cells by the immune system 12-14 .”
From A complex secretory program orchestrated by the inflammasome controls paracrine senescence (2013) · cites this paper as [14]
Activation of HSCs is the major source of ECM and the key driver of liver fibrosis.
“Activation of hepatic stellate cells (HSCs) is the major source of ECM and the key driver of liver fibrosis [5].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [5]
PCNA and KI67 levels estimate cell cycle phase, with PCNA highest in S phase and KI67 highest in M phase.
“Specifically, the levels of PCNA and KI67 provide an estimation of which cell cycle phase a cell is in, with PCNA being at the highest level in the S phase and KI67 in the M phase9,10 (Fig. 1 B).”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [9]
The Results section on senescent stellate cells calls Ki-67 a proliferation-associated marker, and Experimental procedures lists a Ki67 antibody. Neither passage addresses whether its level identifies a cell-cycle phase. Searches for PCNA and for the claimed S- and M-phase peaks found no supporting passage in our copy; page numbers were not provided. (LLM, conf=0.72)
Experimental — accuracy not yet measured18-month-old AP-treated ATTAC mice repaired cutaneous wounds when drug administration was suspended during healing.
“Consistent with a beneficial role of senescent cells only for the duration of wound repair 6 - 8 , 18-month-old AP-treated ATTAC mice repaired cutaneous wounds when drug administration was suspended during healing (Extended Data Fig. 10ac).”
From Naturally occurring p16Ink4a-positive cells shorten healthy lifespan (2016) · cites this paper as [7]
The Animals and Results sections describe mice studied for liver fibrosis, not AP-treated ATTAC mice or cutaneous wound repair. The Discussion suggests that senescence may be relevant to other wound-healing responses, but our copy does not report the specific wound-healing observation; I searched for cutaneous wound repair and senescence. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe SASP includes chemokines and cytokines that activate immune cells to specifically target and eventually clear senescent cells from tissues.
“The SASP also includes several chemokines and cytokines that activate immune cells to specifically target and eventually clear senescent cells from tissues”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [85]
Factors secreted by senescent cells can stimulate the immune system to suppress tumorigenesis and promote repair of damaged tissues.
“these secreted factors can stimulate the immune system to both suppress tumorigenesis and promote optimal repair of damaged tissues when senescent cells are removed after their beneficial actions (15–17).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [15]
This pathway can positively contribute to normal development and wound healing.
“This pathway can positively contribute to normal development and wound healing (15, 17, 61, 62).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [15]
The studies showing roles of senescence in limiting myocardial and liver fibrosis, promoting skin healing, and embryonal development focused on acute organ injury, not chronic processes such as atherosclerosis.
“However, these studies focused on the function of senescence in acute organ injury, not in chronic processes such as atherosclerosis.”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [207]
Cellular senescence has roles in limiting myocardial and liver fibrosis, promoting skin healing, and in embryonal development.
“Experimental evidence shows that cellular senescence has roles in limiting myocardial206 and liver207 fibrosis, promoting skin healing,82 as well as in embryonal development,208 which have to be considered.”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [207]
Senescent cells play beneficial roles during embryonic development, tumor suppression, wound healing, and tissue repair.
“Recent data indicates that senescent cells play a variety of beneficial roles during processes such as embryonic development, tumor suppression, wound healing and tissue repair (Krizhanovsky et al., 2008, Muñoz-Espín et al., 2013, Demaria et al., 2014, Ritschka et al., 2017).”
From Telomeres and cell senescence—size matters not (2017) · cites this paper as Krizhanovsky et al., 2008
Elimination of senescent cells by NK cells is needed to restrain liver fibrosis and return the liver to a predamaged state following short-term damage.
“Elimination of these senescent cells by NK cells is needed to restrain liver fibrosis and return the liver to a predamaged state following short‐term damage”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Krizhanovsky et al, 2008
In liver fibrosis, activated stellate cells become senescent and exhibit activation of DDR.
“In liver fibrosis activated stellate cells become senescent and exhibit activation of DDR.”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Krizhanovsky et al, 2008
In a mouse model of carbon tetrachloride-induced liver fibrosis, accumulation of senescent cells limits fibrosis.
“In a mouse model of carbon tetrachloride-induced liver fibrosis, the accumulation of senescent cells also functions to limit fibrosis [125].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [125]
The SASP of senescent activated HSCs attracts innate immune cells that eliminate these cells and help resolve fibrosis.
“The SASP also attracts innate immune cells that in turn eliminate the senescent HSCs and facilitate the resolution of fibrosis 94,120”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [120]
In a CCl4-induced mouse liver fibrosis model, activated hepatic stellate cells become senescent and display a SASP including extracellular matrix degrading enzymes and proinflammatory cytokines.
“activated HSCs become senescent, exhibiting a typical SASP, including the expression of extracellular matrix degrading enzymes and proinflammatory cytokines.”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [120]
Senescence of hepatic stellate cells regulates fibrosis via the SASP.
“This was the first study to show that hepatic stellate cell senescence controls fibrosis through the SASP.”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [120]
NK cells can recognize and eliminate senescent cells in vivo.
“and recent evidence indicates that NK cells can recognize and eliminate senescent cells in vivo [43, 44].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [43]
Unlike chronic senescence, the acute induction of cellular senescence represents a transient physiological response during embryonic development and adult tissue homeostasis.
“Indeed, unlike chronic senescence (i.e., accumulation of deleterious senescent cells with aging), the acute induction of cellular senescence represents a transient physiological response during embryonic development [27,28] and adult tissue homeostasis (e.g., to facilitate tissue repair after liver damage, in skin fibrosis, and wound healing) [29,30,31].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [29]
Recruitment and activation of T cells and natural killer cells at senescent cells in tumor microenvironment or altered macrophage polarization promote removal of senescent or damaged cells.
“Recruitment and activation of T cells and natural killer cells at the location of senescent cells in the tumor microenvironment or altered polarization of macrophages promote the removal of senescent or damaged cells [29,358,359,360].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [29]
Senescence-associated secretory phenotype factors aid wound healing by attracting immune cells that remove dead cells, supporting angiogenesis, restricting fibrosis, and promoting wound closure.
“SASP has recently been shown to have a beneficial effect on wound healing by recruiting immune cells to clear dead cells, promote angiogenesis, limit fibrosis, and stimulate wound closure (100, 111, 112).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [112]
Immune surveillance of senescent cells is executed by different immune cells such as macrophages, natural killer cells and cytotoxic T cells in cancer and chronic liver cirrhosis.
“Mounting evidence demonstrates that immune surveillance of senescent cells is executed by different immune cells such as macrophages, natural killer (NK) cells and cytotoxic T cells in cancer [5,130] and chronic liver cirrhosis [20].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [20]
Senescence-activated hepatic stellate cells upregulate cell-surface MICA and ULBP2, ligands of activating receptor NKG2D on NK cells.
“For example, senescence-activated hepatic stellate cells upregulate cell-surface MICA and ULBP2, ligands of activating receptor NKG2D on NK cells [20].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [20]
NK cells are involved in elimination of senescent cells through interaction between activating NKG2D receptor and its ligands expressed on senescent cells.
“NK cells are involved in the elimination of senescent cells through interaction between the activating NKG2D receptor and its ligands expressed on senescent cells.”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [20]
YT human NK cell line preferentially destroys senescent IMR-90 fibroblasts.
“the YT human NK cell line preferentially destroys senescent IMR-90 fibroblasts [20].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [20]
NK cell activation by polyinosinic-polycytidylic acid decreases senescent cell number in liver in vivo, leading to reduced liver fibrosis.
“NK cell activation by polyinosinic-polycytidylic acid [152] decreases the senescent cell number in the liver in vivo, leading to reduced liver fibrosis [20].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [20]
The small fraction of senescent HSCs may be in part attributable to immunosurveillance of senescent cells by immune cells that can rapidly remove senescent cells to prevent accumulation in vivo.
“This may be in part attributable to the immunosurveillance of senescent cells by immune cells that can rapidly remove senescent cells to prevent the accumulation of senescent cells in vivo.34”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [34]
The SASP is involved in valuable physiological processes such as promoting tissue repair, fine-tuning development of embryonic structures, and stimulating immune surveillance.
“Furthermore, the SASP is involved in valuable physiological processes such as promoting tissue repair,18–20 fine-tuning the development of embryonic structures,21–23 and stimulating immune surveillance.24,25”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [20]
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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
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“senescent cells, including impaired wound healing or fibrosis during liver regeneration (Krizhanovsky et al., 2008; Demaria et al., 2014).”
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 · see citing works
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Feedback between p21 and reactive oxygen production is necessary for cell senescence
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InfluentialThe DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
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BackgroundMethodResultInfluentialSelf-citationHepatic Stellate Cells and Liver Fibrosis
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The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration.
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Self-citationA guide to assessing cellular senescence <i>in vitro</i> and <i>in vivo</i>
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- Authors
- Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Universidade de São Paulo (BR)
- Howard Hughes Medical Institute (US)
- NYU Langone Health (US)
- Corresponding author
- Lowe, Scott W.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 134
- Issue
- 4
- Pages
- 657-667
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3073300
- OpenAlex
- W1570233039
- Semantic Scholar
- ce5e5a42201ddcfa8349e137ece0309db96e4616
- Cited by
- 2,029
- References
- 34
- Citations by year
- 2026: 114 · 2025: 135 · 2024: 153 · 2023: 135 · 2022: 156 · 2021: 170 · 2020: 154 · 2019: 146 · 2018: 137 · 2017: 126 · 2016: 125 · 2015: 90 · 2014: 88 · 2013: 83 · 2012: 64
- FWCI
- 35.83
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-10-03)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R56AG016379, AG-16379, R01AG016379)
- National Cancer Institute (P01CA013106, P30CA008748)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- cellular senescence, activated hepatic stellate cells, liver fibrosis, liver cirrhosis, extracellular matrix deposition, natural killer cells, immune surveillance, cell cycle exit
- MeSH terms
- Animals, Carbon Tetrachloride, Cells, Cultured, Female, Fibroblasts, Humans, Killer Cells, Natural, Liver, Liver Cirrhosis, Liver Cirrhosis, Experimental, Cellular Senescence, Mice
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