Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
Open accessAbstract
Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI). Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a 'senolytic' pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type- and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents.
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UBX0101 was recently found to selectively eliminate senescent cells.
“a senolytic (UBX0101) that was recently found to selectively eliminate SnCs16,29.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [16]
The Abstract identifies ABT263—not UBX0101—as the senolytic this study found to selectively kill senescent cells. A search of our copy for UBX0101 found no passage identifying it as a drug studied here. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredABT-263 can cause thrombocytopenia and neutropenia even after brief exposure.
“N can cause thrombocytopenia and neutropenia, even after brief exposures57,88–91”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [88]
The paper’s concluding discussion (indexed under Abstract; page unavailable) identifies thrombocytopenia and neutropenia as common, transient toxicities of ABT263 treatment in patients. It does not say that either occurs after brief exposure. The Online Methods describe short treatment cycles in mice but do not link those cycles to these toxicities. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSenescent cells resist apoptotic death more than normal cells because survival pathways, including BCL-2 family antiapoptotic proteins, are upregulated, even after exogenous stress.
“Senescent cells have increased resistance to apoptotic cell death owing to upregulation of cell survival pathways, including the BCL-2 family of antiapoptotic proteins, even on exogenous stress exposure14,15”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [15]
In the passage labeled Abstract (page unavailable), the paper reports increased BCL-xL in senescent cells and experiments suggesting that BCL-2 and BCL-xL protect them from apoptosis. It does not establish greater resistance to apoptotic death than normal cells after exogenous stress exposure; it also reports no increase in BCL-2 expression. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSenescent cells often increase negative regulators of apoptosis, such as BCL-2, BCL-W, and BCL-XL, making them resistant to apoptosis-inducing signals.
“Senescent cells frequently upregulate negative modulators of apoptosis, including members of the BCL-2 family (including BCL-2, BCL-W and BCL-XL), which confers resistance to apoptosis-inducing signals14,15.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [15]
The paper’s results passage (indexed under Abstract; page unavailable) reports increased anti-apoptotic BCL-xL in senescent cells and suggests that BCL-2 and BCL-xL protect them from apoptotic death. It does not report increased BCL-2—indeed, it says the observed sensitivity did not correlate with increased BCL-2—or establish increased BCL-W. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe p16-3MR transgenic mouse harbors a p16INK4a promoter driving expression of a fusion protein containing Renilla luciferase and monomeric red fluorescent protein domains, as well as a truncated form of herpes simplex virus 1 thymidine kinase.
“we used the p16-3MR transgenic mouse, which harbors a p16INK4a (Cdkn2a) promoter driving the expression of a fusion protein containing synthetic Renilla luciferase and monomeric red fluorescent protein domains, as well as a truncated form of herpes simplex virus 1 thymidine kinase (HSV-TK)15,16.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [16]
The passage labeled Abstract (page unavailable) describes p16-3MR mice as carrying a reporter driven by the Cdkn2a/p16 promoter and identifies Renilla luciferase, monomeric red fluorescent protein, and HSV-TK as its components. It does not specify that the luciferase is synthetic or that HSV-TK is truncated, so those details are not supported by our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
GCV may not reach the bone when injected intra-articularly, and systemic administration may be required.
“suggesting that GCV may not reach the bone when injected intra-articularly and that systemic administration may be required16.”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [16]
The Online Methods (page unavailable) report that GCV was given by intraperitoneal injection, and the results passage reports depletion of senescent cells in irradiated mice. The paper does not examine intra-articular injection or whether GCV reaches bone by that route, so it does not establish that systemic administration may be required. (LLM, conf=0.78)
Experimental — accuracy not yet measuredStudies have identified oncogene-induced, irradiation-induced, and ageing-induced accumulation of senescent cells in bone marrow.
“Studies have identified oncogene-induced, irradiation-induced and ageing-induced accumulation of senescent cells in the bone marrow92–94.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [92]
The paper reports senescence markers in bone-marrow hematopoietic stem cells after irradiation and says treatment clears senescent stem cells from the bone marrow of aged mice. It also induces oncogene (Ras)-driven senescence, but in cultured WI-38 cells, not bone marrow. Thus it does not support all three causes of bone-marrow senescent-cell accumulation attributed to the citation cluster. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAgents that target Bcl-xL, including navitoclax (ABT263), A1331852, and A1155463, are senolytic, at least with some types of senescent cells.
“We and others found that agents that target Bcl-xL, including navitoclax (ABT263), A1331852, and A1155463, are senolytic, at least with some types of senescent cells [18,57,58].”
From Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (2019) · cites this paper as [57]
The Abstract identifies ABT263 as an inhibitor of BCL-2 and BCL-xL that selectively kills senescent cells. Our copy does not report senolytic activity for A1331852 or A1155463; it also reports that a different BCL-xL inhibitor, WEHI539, did not selectively kill the senescent cells tested when used alone. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSenescent cells accumulate with ageing and age-associated diseases, limiting lifespan and healthspan in mice.
“Senescent cells accumulate with ageing and age-associated diseases, limiting lifespan and healthspan in mice11–16.”
From Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (2023) · cites this paper as [13]
The Abstract (page not provided) says senescent cells accumulate with age and that clearing them delays several age-associated disorders in a progeroid mouse model. It describes extending healthspan as a prospect, not a demonstrated outcome, and does not report that senescent cells limit mouse lifespan. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevious studies demonstrated that senolytics showed different efficacies across senescent cell culture models using bulk RNA-Seq.
“Previous studies demonstrated that senolytics showed different efficacies across senescent cell culture models (based on different cell types and senescence inducers) using bulk RNA-Seq technologies [4, 16].”
From Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction (2025) · cites this paper as [4]
The paper’s Abstract describes earlier senolytics as cell type–selective and reports testing ABT263 across different cell types and senescence inducers. It says ABT263 killed senescent cells regardless of how senescence was induced, and it describes cytotoxicity testing rather than bulk RNA-Seq. Thus it supports variation in cell-type selectivity, but not the claimed RNA-Seq-based demonstration across those models. (LLM, conf=0.83)
Experimental — accuracy not yet measuredCellular senescence encompasses heterogeneous cellular states triggered by prolonged cell stress resulting in irreversible arrest of proliferation and permanent changes to cell function in vivo.
“Cellular senescence, a central hallmark of aging,13,14 encompasses heterogeneous cellular states triggered by prolonged cell stress resulting in the irreversible arrest of proliferation and permanent changes to cell function in vivo.15,16,17,18,19”
From Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex (2026) · cites this paper as [15]
The ONLINE METHODS > Cells section (page unavailable) describes senescence induced by replicative exhaustion, irradiation, and oncogenic Ras, and reports that replicatively senescent cells stopped dividing. The Abstract (page unavailable) reports persistent reductions in the function of irradiated hematopoietic stem cells. These passages support multiple triggers, proliferative arrest, and altered function, but do not establish heterogeneous cellular states, irreversible arrest, or permanent functional changes in vivo as general features of senescence. (LLM, conf=0.82)
Experimental — accuracy not yet measuredNavitoclax treatment in mice lowers senescent cell burden, improves radiation-induced hematopoietic stem cell dysfunction, and alleviates osteoarthritis.
“Treating mice with navitoclax reduces Snc burden, alleviates radiation-induced hematopoietic stem cell dysfunction (28), and improves osteoarthritis (10).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [28]
The p16-3MR mouse strain allows selective follow and removal of senescent cells after anterior cruciate ligament transection.
“This mouse strain allowed us to selectively follow and remove SnCs after anterior cruciate ligament transection (ACLT).”
From Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment (2017) · cites this paper as [16]
Navitoclax-related depletion of senescent cells rejuvenated the regenerative capacity of aged haematopoietic stem cells and muscle stem cells in mice without cancer.
“Navitoclax- related depletion of senescent cells also 'rejuvenated' the regenerative capacity of aged haematopoietic stem cells and muscle stem cells in mice without cancer 203 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [203]
Inhibitors against BCL-2/BCL-XL are recognized as senolytic drugs.
“In a similar mechanistic approach, inhibitors against B-cell lymphoma-2 (BCL-2)/BCL-XL are also recognized as senolytic drugs [113].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [113]
NRTIs can be categorized as "senostatic" agents, to contrast them from "senolytic" treatments that remove senescent cells from tissues.
“Hence, NRTIs can be categorized as “senostatic” agents, to contrast them from “senolytic” treatments that remove senescent cells from tissues21,22.”
From L1 drives IFN in senescent cells and promotes age-associated inflammation (2019) · cites this paper as [21]
Senescent cells have elevated vulnerability to inhibitors of pro-survival BCL2 family members, particularly BCL-XL, reflecting elevated dependence on these proteins for survival.
“In this context, one promising senolytic regimen relies on the elevated vulnerability of senescent cells to inhibitors of pro-survival BCL2 family members (in particular BCL-XL), reflecting the elevated dependence of senescent cells on these proteins for survival [971–973].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [971]
ABT-737 and navitoclax bind the inhibitory pockets of BCL-2 family proteins, blocking their anti-apoptotic function.
“The senolytic molecules ABT-737 (37) and navitoclax (ABT-263) (93) occupy the inhibitory binding regions of members of the BCL-2 family of proteins, thereby canceling their antiapoptotic activity.”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [93]
Navitoclax clears senescent cells appearing in early atherosclerotic plaques and after sublethal irradiation in skeletal muscle and bone marrow.
“Navitoclax treatment has been shown to eliminate senescent cells that arise in early atherosclerotic plaques (30) and upon sublethal irradiation in both skeletal muscle and the bone marrow (93).”
From Cellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives (2018) · cites this paper as [93]
Senolytic drugs are more effective against particular senescent cell types in vitro, and less effective against others, for unclear reasons.
“Senolytic drugs were known to be more effective against particular senescent cell types in vitro, and less effective against others, for unclear reasons.42,174–185”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [178]
In addition to BCL-2 family members, SCAPs are mediated by SRC family tyrosine kinases and pro-survival pathways related to serpin, heat shock protein and p21CIP1.
“In addition to BCL-2 family members, SCAPs are mediated by SRC family tyrosine kinases as well as pro-survival pathways related to serpin, heat shock protein and p21CIP1 (refs.99–104).”
From COVID-19 and cellular senescence (2023) · cites this paper as [100]
Senescent cell elimination can increase the proliferative capacity of stem cells and hence support tissue regeneration.
“Senescent cell elimination can indeed increase the proliferative capacity of stem cells and hence support tissue regeneration”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Chang et al, 2016
ABT-263 is a senolytic that inhibits BCL-2 family anti-apoptotic proteins, which are typically upregulated in senescent cells.
“ABT‐263 is one senolytic and functions to inhibit the BCL‐2 family of anti‐apoptotic proteins, which are typically upregulated in senescent cells (Zhu et al, 2016; Chang et al, 2016).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Chang et al, 2016
ABT263 is one of the most potent and broad-spectrum senolytic agents identified to date.
“ABT263 (also known as navitoclax), a Bcl-2 and Bcl-xl dual inhibitor23,24, is one of the most potent and broad-spectrum senolytic agents identified to date16–18.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
PZ might be more effective than ABT263 in rejuvenating aged HSCs under this less intensive treatment regimen because previous study showed ABT263 was more effective in rejuvenating aged HSCs under a more intensive treatment schedule.
“Again, these findings suggest that PZ might be more effective than ABT263 in rejuvenating aged HSCs under this less intensive treatment regimen because our previous study showed that ABT263 was more effective in rejuvenating aged HSCs under a more intensive treatment schedule16.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
At a more intensive dosing schedule, which consisted of two cycles of 7 daily IP injections of the same dose of either agent, ABT was equally effective to PZ in clearing senescent cells in multiple organs in naturally aged mice.
“However, at a more intensive dosing schedule, which consisted of two cycles of 7 daily IP injections of the same dose of either agent, ABT was equally effective to PZ in clearing SCs in multiple organs in naturally aged mice as shown in our previous studies (Supplementary Fig. 8)16.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
Both senescent cells and platelets, but not non-senescent cells, are primarily dependent on Bcl-xl for survival.
“Because both SCs and platelets, but not NCs, are primarily dependent on Bcl-xl for survival16–18,24–27 (Supplementary Fig. 1h), we evaluated the effects of PZ compared with ABT263 on the viability of WI38 NCs (Fig. 1g, left panel), IR-SCs (Fig. 1g, middle panel), and platelets (Fig. 1g, right panel).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
ABT263 is highly toxic to both WI38 IR-SCs and platelets.
“As reported, ABT263 was highly toxic to both WI38 IR-SCs (Fig. 1g, middle panel) and platelets16–18,24–27 (Fig. 1g, right panel; Supplementary Fig. 2).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
Clearance of senescent cells with ABT263 rejuvenated HSCs to reduce age-associated myeloid skewing and HSC expansion in prematurely aged mice induced by TBI and naturally aged mice.
“Our previous studies have shown that clearance of SCs with ABT263 rejuvenated HSCs to reduce age-associated myeloid skewing and HSC expansion in prematurely aged mice induced by TBI and naturally aged mice16.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
Senescent cells were induced and validated as previously described.
“SCs were induced and validated as previously described13,14,16.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
PZ can selectively induce apoptosis in senescent cells, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to non-senescent cells that are less sensitive to Bcl-xl inhibition than senescent cells.
“Therefore, PZ can selectively induce apoptosis in SCs, but not platelets, which are dependent on Bcl-xl for survival while having minimal toxicity to NCs that are less sensitive to Bcl-xl inhibition than SCs16–18,24–27.”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
Inhibition of Bcl-2 and/or Bcl-w can potentiate the cytotoxicity of Bcl-xl inhibition against senescent cells as seen in previous studies with the dual Bcl-2/w and Bcl-xl inhibitors ABT737 and ABT263.
“However, inhibition of Bcl-2 and/or Bcl-w can potentiate the cytotoxicity of Bcl-xl inhibition against SCs as seen in previous studies with the dual Bcl-2/w and Bcl-xl inhibitors ABT737 and ABT263 (refs. 16,17).”
From Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity (2020) · cites this paper as [16]
Inhibitors of the BCL-2 family, such as ABT-263 and ABT-737, reduce senescent hematopoietic and muscle stem cells in radiation-exposed and aged mice and senescent cells in the lung and epidermis.
“Inhibitors of the BCL-2 family, such as ABT-263 (navitoclax) and ABT-737, have been shown to reduce senescent hematopoietic and muscle stem cells in radiation-exposed and aged mice (Chang et al., 2016) and senescent cells in the lung and epidermis (Yosef et al., 2016).”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as Chang et al., 2016
Cellular senescence occurs not only in vitro but also in various tissues in vivo.
“Cellular senescence occurs not only in vitro (i.e., cell culture models), but also in various tissues in vivo [13,14,15,16].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Senescent cells accumulate in different tissues and organs where they have distinct physiological and pathological functions.
“Senescent cells accumulate in different tissues and organs where they have distinct physiological and pathological functions.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Elimination of senescent cells can promote stem cell proliferation and delay the appearance of aging features.
“Importantly, elimination of senescent cells can promote stem cell proliferation and delay the appearance of aging features [13,14,15].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Clearing senescent cells from adult mice by ABT263 or inducible transgene rejuvenates hematopoietic and muscle stem cells, slows age-related disease, and increases lifespan.
“Clearing senescent cells from adult mice by inducing apoptosis with the drug ABT263 or an inducible transgene rejuvenates hematopoietic and muscle stem cells, slows the onset of age-related disease, and increases lifespan (Baker et al., 2016; Chang et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Chang et al., 2016
Senescence is associated with upregulation of anti-apoptotic proteins of the BCL-2 family, particularly BCL-2, BCL-Xl, and BCL-W.
“Senescence also is associated with upregulation of anti-apoptotic proteins of the BCL-2 family, particularly BCL-2, BCL-Xl, and BCL-W [14,15,143,144]”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Senescent cells rely on upregulation of pro-survival pathways, such as BCL-2 and Ephrins, that actively inhibit apoptosis.
“For this, senescent cells rely on the upregulation of pro-survival pathways (e.g., BCL-2 and Ephrins) that actively inhibit apoptosis [3,14,15].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Inhibition of anti-apoptotic BCL2, BCL-W, and BCL-XL proteins induces apoptosis of senescent cells and their elimination in mice.
“For example, inhibition of the anti-apoptotic BCL2, BCL-W, and BCL-XL proteins induces apoptosis of senescent cells and their elimination in mice [3,14].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [14]
Pharmacologically targeting senescent bone marrow cells has beneficial effects.
“pharmacological targeting of senescent bone marrow cells has been shown to have beneficial effects.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [59]
BCL2 inhibitors can directly eliminate senescent cells.
“Evidence that BCL2 inhibitors can directly eliminate senescent cells (Chang et al., 2016; Yosef et al., 2016) suggests that combining this with other cancer therapies in a sequential manner might be useful.”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Chang et al., 2016
Oral administration of ABT263 in sublethally irradiated mice and naturally aged mice resulted in mitigation of premature ageing of the haematopoietic system induced by total body irradiation and rejuvenation of aged haematopoietic stem cells.
“In 2016, Chang and colleagues 30 showed that oral administration of ABT263 in sublethally irradiated mice and naturally aged mice resulted in a mitigation of premature ageing of the haematopoietic system induced by total body irradiation and a rejuvenation of aged haematopoietic stem cells.30”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [30]
Clearance of chronically senescent cells from aged or irradiated animal models benefits multiple organs, including the kidney.
“Clearance of chronically senescent cells from aged or irradiated animal models benefits multiple organs, including the kidney.6,30”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [30]
Fisetin and navitoclax kill senescent fibroblasts and endothelial cells but have limited effect on senescent preadipocytes.
“Both fisetin and navitoclax kill senescent fibroblasts and endothelial cells, yet have limited effect on senescent preadipocytes [20,21].”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [21]
All current senolytics have distinct efficacy on diverse senescent cell populations.
“It is now evident that all current senolytics have distinct efficacy on diverse senescent cell populations.”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [21]
In a phase II study of ABT263 for advanced and recurrent small-cell lung carcinoma, transient thrombocytopenia and neutropenia were reported as side-effects.
“in a phase II study of ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL2 and BCL-xL)19 for the treatment of advanced and recurrent small-cell lung carcinoma patients, transient thrombocytopenia and neutropenia were reported as side-effects15.”
From A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells (2020) · cites this paper as [19]
Senolytic drugs identified to date were not discovered by a truly unbiased high-throughput screening method and appear to have limitations in clinical applications.
“However, the senolytic drugs identified to date were not discovered by a truly unbiased high-throughput screening (HTS) method, and thus appear to have limitations in clinical applications15,17–19.”
From A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells (2020) · cites this paper as [19]
The percentage of isolated satellite cells positive for p16 by immunostaining and the number of DNA double-strand breaks per satellite cell were lower from mice treated with ABT263 compared to vehicle.
“The percentage of isolated satellite cells positive for p16 by immunostaining and the number of DNA double-strand breaks per satellite cell were lower from mice treated with ABT263 compared to vehicle (Chang et al., 2016).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Chang et al., 2016
Genetic or chemical ablation of senescent cells in mouse models delays the onset of age-related disorders, including cancer, leading to increased life-spans and promoting tissue rejuvenation in late life.
“Importantly, genetic or chemical ablation of senescent cells in mouse models delays the onset of age-related disorders, including cancer, leading to increased life-spans and promoting tissue rejuvenation in late life.36–38”
From Paracrine roles of cellular senescence in promoting tumourigenesis (2018) · cites this paper as [36]
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- Authors
- Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., Luo, Y., Wang, X., Aykin-Burns, N., Krager, K., Ponnappan, U., Hauer-Jensen, M., Meng, A., & Zhou, D.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Buck Institute for Research on Aging (US)
- University of North Carolina at Chapel Hill (US)
- Gladstone Institutes (US)
- Corresponding author
- Zhou, Daohong
- ORCID
- Venue
- Nature Medicine
- Published
- 2015-12-14
- Volume
- 22
- Issue
- 1
- Pages
- 78-83
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4762215
- OpenAlex
- W2224886002
- Cited by
- 1,819
- References
- 42
- Citations by year
- 2026: 149 · 2025: 168 · 2024: 200 · 2023: 192 · 2022: 199 · 2021: 210 · 2020: 206 · 2019: 150 · 2018: 161 · 2017: 111 · 2016: 69 · 2015: 1
- FWCI
- 83.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (5r01ag024379-15)
- National Institute on Aging (R01-AG024379, R37AG009909)
- National Cancer Institute (R01CA122023)
- National Institute of General Medical Sciences (P20GM109005)
- National Institute of Allergy and Infectious Diseases (R01AI080421)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- senolytics, navitoclax, senescent cells, hematopoietic stem cells, muscle stem cells, BCL-2 inhibition, apoptosis, total body irradiation, premature aging, tissue rejuvenation, healthspan, anti-aging agents
- MeSH terms
- Aniline Compounds, Animals, Antineoplastic Agents, Antiviral Agents, B-Lymphocytes, Cell Cycle, Cell Line, Cell Survival, Colony-Forming Units Assay, DNA Damage, Hematopoietic Stem Cells, Humans, Microscopy, Rejuvenation, RNA, Messenger, Sulfonamides, Whole-Body Irradiation, Blotting, Western, Ganciclovir, Cellular Senescence, Apoptosis, Muscle, Skeletal, Proto-Oncogene Proteins c-bcl-2, Cyclin-Dependent Kinase Inhibitor p16, Myoblasts, bcl-X Protein, Mice, Gene Knockdown Techniques
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