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        <title>Frontiers in Aging | Cellular Senescence section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/aging/sections/cellular-senescence</link>
        <description>RSS Feed for Cellular Senescence section in the Frontiers in Aging journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-05-10T22:16:25.345+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2026.1754569</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2026.1754569</link>
        <title><![CDATA[Ectoine attenuates H2O2-Induced cellular senescence in human keratinocytes and endothelial cells by modulating the p53/p21 and p16 pathways]]></title>
        <pubdate>2026-02-26T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Meini Li</author><author>Jingyue Zhang</author><author>Wenke Yang</author><author>Zengqiang Miao</author><author>Yanran Pai</author><author>Yi Yi</author><author>Jie Shuang</author><author>Xiang Gao</author><author>Yongzhen Li</author>
        <description><![CDATA[BackgroundEctoine ((S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid) is a major compatible solute found in halophilic microorganisms from salt lakes. The anti-cellular senescence effect and skin safety of Ectoine on H2O2-induced oxidative stress senescence in HaCaT cells and EA. hy926 endothelial cells were evaluated through a series of in vitro assays.MethodsAn oxidative stress senescence model was established using H2O2 in HaCaT and EA. hy926 cells pretreated with various concentrations of Ectoine. Cell viability was assessed using the CCK-8 assay, proliferative capacity was evaluated with the EdU assay, and senescence status was determined by SA-β-gal staining. Intracellular ROS levels were measured using a DCFH probe, and cell death was analysed by flow cytometry. The expression of senescence-related markers was evaluated at the transcriptional and protein levels: The mRNA levels of TP53, CDKN1A (encoding p21), CDKN2A (encoding p16), MMP2, and MMP9 were measured by qRT‒PCR, while their corresponding protein products (p53, p21, and p16) were analysed by Western blotting. Lamin B1 expression was examined by immunofluorescence.ResultsExposure to H2O2 successfully induced cellular senescence, as evidenced by increased SA-β-gal activity, elevated ROS levels, and upregulated expression of senescence-associated markers (TP53, CDKN1A, CDKN2A, MMP2, and MMP9), along with decreased Lamin B1 expression. Ectoine pretreatment significantly attenuated these senescence phenotypes in a concentration-dependent manner, with 0.50 μmol/L identified as the most effective concentration. At this dosage, Ectoine enhanced cell viability, reduced ROS accumulation, and suppressed cell death without causing cytotoxicity. Mechanistically, Ectoine downregulated the expression of the p53/p21 and p16 pathway components, thereby inhibiting cell cycle arrest.ConclusionEctoine exerts potent anti-senescence effects in H2O2-induced models of skin-related cell senescence, primarily by modulating the p53/p21 and p16 signalling pathways and reducing oxidative damage. These findings may support further exploration of its potential application in anti-cellular senescence research.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1721744</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1721744</link>
        <title><![CDATA[Cellular senescence in age-related cardiovascular disease: past and future]]></title>
        <pubdate>2026-01-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Xiang Wu</author><author>Qingyu Zhou</author><author>Yingying Huang</author><author>Wangqing Jiang</author><author>Jianming Zhou</author><author>Ke Qian</author><author>Yinchen Pan</author><author>Zuyao Wu</author><author>Jingjun Zhang</author><author>Madinai Aimaiti</author><author>Qi Zhou</author><author>Feizhou Lv</author><author>Yong Lin</author><author>Shaomin Li</author><author>Shuying Chen</author>
        <description><![CDATA[Cellular senescence is a distinct and definable biological state characterized by irreversible cell cycle arrest, accompanied by the activation of the DNA damage response (DDR), telomere shortening, the senescence-associated secretory phenotype (SASP), and metabolic dysfunction. While senescent cells represent only a small fraction of the total cell population in tissues, they exert a disproportionate and systemic impact on age-related cardiovascular disease (CVD) through paracrine and endocrine mechanisms. This review moves beyond a descriptive list of pathways and instead proposes a unified framework centered on how a small number of senescent cells can reprogram the cardiovascular microenvironment. We focus on the SASP as the central executor of this systemic effect, disseminating local senescence and driving chronic inflammation, fibrosis, and dysfunction across major cardiovascular cell types (cardiomyocytes, endothelial cells, fibroblasts, smooth muscle cells). We integrate key regulatory networks such as mTOR, AMPK, and Sirtuins that modulate the SASP and the senescent state. Furthermore, we discuss the translational promise of senolytics (agents that clear senescent cells) and senomorphics (agents that suppress the SASP) as novel strategies for delaying cardiovascular aging and treating age-related CVD, providing a forward-looking perspective on targeting senescence to promote cardiovascular health. Current research challenges include mechanistic complexity and limitations of animal models and in vitro systems. In the future, it is necessary to combine single-cell sequencing, metabolic intervention, and interdisciplinary technologies to analyze the heterogeneity of cellular aging, and develop early warning and precision treatment strategies based on aging biomarkers, so as to provide new ideas for delaying cardiovascular aging.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1657947</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1657947</link>
        <title><![CDATA[Celastrol attenuates diabetic kidney disease progression by repressing senescence of renal tubular epithelial cells]]></title>
        <pubdate>2025-11-27T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yajun Zhang</author><author>Zewei Sun</author><author>Weixue Meng</author><author>Siqi Lei</author><author>Jingyong Sun</author><author>Yixuan Tang</author><author>Xiaodong Mu</author>
        <description><![CDATA[BackgroundRecent investigations across both animal models and human cohorts increasingly highlight cellular senescence as a critical pathological process driving the development and progression of diabetic nephropathy (DN). The detrimental impact of senescent cells on DN advancement stems from a range of underlying mechanisms, notably telomere attrition, compromised mitochondrial function, dysregulated autophagy, chronic inflammatory responses, altered mTOR signaling and Sirtuin activity, and the release of pro-coagulant factors. Diabetic kidney disease (DKD) is a common and serious complication in diabetic patients, closely associated with high glucose-induced defects in kidney cells. Currently the clinical treatment of DKD disease is still a challenge. Celastrol, a compound derived from Tripterygium wilfordii, has shown significant therapeutic effects on DKD, but the specific mechanisms remain unclear.MethodsWe established in vitro and in vivo models of DKD using human renal tubular epithelial cells (HK-2) and Sprague-Dawley (SD) rats. The effects of celastrol on glucose-induced oxidative damage to HK-2 cells and kidney injury in DKD rats were observed. The potential mechanisms were investigated through both in vitro and in vivo experiments.ResultsHigh glucose induced accelerated senescence of HK-2 cells in vitro, and celastrol reversed senescence-associated pathological changes in the cells. Celastrol reduced pro-inflammatory signaling and mitochondrial damage in vitro by inhibiting the phosphorylation of aging- and inflammation-related proteins NF-κB and AKT1. In vivo, celastrol inhibited the phosphorylation of NF-κB and AKT1 in renal tissues, effectively improving renal dysfunction and pathological changes in DKD rats, and reducing disease-related indicators.ConclusionCelastrol may be a promising candidate drug for the treatment of DKD. It can treat DKD by reversing the imbalance of the immune-inflammatory system mediated by the AKT/NF-κB/TNF-α signaling during the progression of the disease and may also delay the progression of DKD through its anti-aging effect.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1583288</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1583288</link>
        <title><![CDATA[Membrane transporter progressive ankylosis protein homologue (ANKH/Ank) partially mediates senescence-derived extracellular citrate and is regulated by DNA damage, inflammation, and ageing]]></title>
        <pubdate>2025-06-04T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Emma Naomi James</author><author>Muy-Teck Teh</author><author>Yufeng Li</author><author>Christine Wagner-Bock</author><author>Zahra Falah Al-Khateeb</author><author>Lee Peng Karen-Ng</author><author>Terry Roberts</author><author>Linnea Synchyshyn</author><author>Amy Lewis</author><author>Ana O’Loghlen</author><author>Andrew Silver</author><author>Adina Teodora Michael-Titus</author><author>Mark Bennett</author><author>Jacob Guy Bundy</author><author>Maria Elzbieta Mycielska</author><author>Eric Kenneth Parkinson</author>
        <description><![CDATA[IntroductionA considerable body of recent evidence supports citrate transport as a major regulator of organismal lifespan and healthspan. Citrate accumulates outside senescent cells in vitro and in vivo. However, the detailed mechanism of senescent cell extracellular citrate (EC) accumulation is not clear.MethodsEC following various drug and cytokine treatments was measured in human fibroblast and keratinocyte conditioned medium by gas chromatography/mass spectroscopy and liquid chromatography/mass spectroscopy. Membrane transporters in similar human fibroblasts cultures were measured by western blotting and more extensively by reverse transcription and quantitative polymerase chain reaction (qPCR) in human fibroblasts, keratinocytes, myoblasts, adipocytes and astrocytes. Mouse tissues were tested for senescence markers and by qPCR, immunofluorescence and immunoFISH telomere associated foci (TAF) staining. Cytokine levels in conditioned medium were measured by the enzyme-linked immunosorbent assay and in mouse brain tissue and plasma samples using the V-PLEX proinflammatory panel 1 mouse kit.Results and DiscussionWe show here that EC is partially mediated by a newly described plasma membrane citrate transporter ANKH/SLC62A1 (progressive human ankylosis -ANKH) in senescent fibroblasts. Analogous to interleukin 6 (IL-6), EC and/or ANKH are regulated by telomere dysfunction, the p38 mitogen-activated kinase axis, transforming growth factor beta and p53, but in contrast not by steroids, sodium butyrate, or Ataxia Telangiectasia Mutated (ATM). ANKH was upregulated in other senescent cell types relevant to ageing but not keratinocytes. In contrast, EC and ANKH were inhibited by interleukin 1α (IL-1α) in dividing and senescent fibroblasts, accompanied by an increase in IL-6 secretion. Loss- and gain of function mutations of ANKH/Ank are associated with disease and interestingly, Ank is also downregulated in both aged mouse liver and brain tissues in parallel with increased senescence markers and several cytokines, suggesting that inflammatory cytokines could inhibit EC production in vivo. These data identify ANKH/Ank as a novel regulator of senescence-derived EC in both humans and mice.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1569422</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1569422</link>
        <title><![CDATA[Analysis of the senescence secretome during zebrafish retina regeneration]]></title>
        <pubdate>2025-04-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Gregory J. Konar</author><author>Kyle T. Vallone</author><author>Tu D. Nguyen</author><author>James G. Patton</author>
        <description><![CDATA[IntroductionZebrafish possess the innate ability to regenerate any lost or damaged retinal cell type with Müller glia serving as resident stem cells. Recently, we discovered that this process is aided by a population of damage-induced senescent immune cells. As part of the Senescence Associated Secretory Phenotype (SASP), senescent cells secrete numerous factors that can play a role in the modulation of inflammation and remodeling of the retinal microenvironment during regeneration. However, the identity of specific SASP factors that drive initiation and progression of retina regeneration remains unclear.Materials and MethodsWe mined the SASP Atlas and publicly available RNAseq datasets to identify common, differentially expressed SASP factors after retina injury. These datasets included two distinct acute damage regimens, as well as two chronic, genetic models of retina degeneration. We identified overlapping factors between these models and used genetic knockdown experiments, qRT/PCR and immunohistochemical staining to test a role for one of these factors (npm1a).ResultsWe discovered an overlapping set of 31 SASP-related regeneration factors across all data sets and damage paradigms. These factors are upregulated after damage with functions that span the innate immune system, autophagic processing, cell cycle regulation, and cellular stress responses. From among these, we show that depletion of Nucleophosmin 1 (npm1a) inhibits retina regeneration and decreases senescent cell detection after damage.DiscussionOur data suggest that differential expression of SASP factors promotes initiation and progression of retina regeneration after both acute and chronic retinal damage. The existence of a common, overlapping set of 31 factors provides a group of novel therapeutic targets for retina regeneration studies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1504977</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1504977</link>
        <title><![CDATA[Human dermal fibroblast senescence in response to single and recurring oxidative stress]]></title>
        <pubdate>2025-03-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Tailynn Y. McCarty</author><author>Cathal J. Kearney</author>
        <description><![CDATA[Introduction: Aging results in an accumulation of damaged cells, which reduces the health of tissues and their regenerative capabilities. In the skin, there are both internal and external drivers of oxidative stress that result in aging phenotypes. Oxidative stress has been used to model senescence in vitro; however, there has been a lack of research determining whether the severity of oxidative stress correlates with senescent phenotypes.Methods: In this work, we compare cellular and secretory responses to a single (500 μM hydrogen peroxide, 2 hours) or recurring dose of hydrogen peroxide (500 μM hydrogen peroxide, 2 hours + 4 × 300 μM hydrogen peroxide each 48 hours). Senescence induction was studied using markers including cell morphology, senescence-associated-beta-galactosidase, absence of apoptosis, and cell cycle inhibition genes. Next, functional studies of the effects of the signaling of these cells were completed, such as vascular potential, keratinocyte proliferation, and macrophage polarization.Results: Fibroblasts exposed to both single and recurring oxidative stress had increased total cell and nucleic area, increased senescence-associated-beta-galactosidase (SABGAL) expression, and they were able to escape apoptosis – all characteristics of senescent cells. Additionally, cells exposed to recurring oxidative stress expressed increased levels of cell cycle inhibitor genes and decreased expression of collagen-I, -III, and -IV. Cytokine profiling showed that the single stressed cells had a more inflammatory secretory profile. However, in functional assays, the recurring stressed cells had reduced vascular potential, reduced keratinocyte proliferation, and increased IL-1β gene expression in unpolarized and polarized macrophages.Discussion: The described protocol allows for the investigation of the direct effects of single and recurring oxidative stress in fibroblasts and their secretory effects on surrounding healthy cells. These results show that recurringly stressed fibroblasts represent a more intense senescent phenotype, which can be used in in vitro aging studies to understand the severity of senescent responses.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1512322</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1512322</link>
        <title><![CDATA[Klotho protects INS-1 pancreatic β-cells from senescence and enhances mitochondrial function]]></title>
        <pubdate>2025-02-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Zhihong Wang</author><author>Yunzhi Ni</author><author>Yan-Ru Lou</author><author>Gerald J. Prud’homme</author><author>Qinghua Wang</author>
        <description><![CDATA[Aging is an important contributing factor for β-cell failure which could lead to the development of type 2 diabetes (T2D). Aging β-cell exhibits signs of senescence and develops senescence-associated secretory phenotype (SASP), causing the senescence and dysfunction of neighboring cells through paracrine action. Klotho is recognized as an anti-aging gene, and the corresponding protein is α-Klotho (KL). KL exerts potent anti-aging effects on multiple cell types, but its role in β-cell aging remains unclear. Here we showed that pancreatic INS-1 cell (a rat insulinoma cell line commonly used to study pancreatic β-cell function) developed the typical hallmarks of senescent cells when treated with doxorubicin in vitro, and this was accompanied by downregulation of endogenous KL expression. Supplementation with exogenous KL protein protected pancreatic INS-1 cell against senescence, as indicated by downregulation of senescent markers and SA-β-gal staining. Notably, these effects were associated with improved mitochondrial ATP production and mitochondrial dynamic balance, as well as reduced ROS production. Our study further revealed that INS-1 cell treated with doxorubicin exhibited a reduced insulin secretion response to glucose stimulation, while supplementation with KL could reverse this effect. Our results indicate the important role of KL in regulating β-cell senescence and provide new mechanistic insights into its role in β-cell aging.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2025.1505063</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2025.1505063</link>
        <title><![CDATA[Inhibition of miMOMP-induced SASP to combat age-related disease]]></title>
        <pubdate>2025-01-29T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Xiaoli Liao</author><author>Zhennan Guo</author><author>Mouhai He</author><author>Yichun Zhang</author>
        <description><![CDATA[Cellular senescence, first described in 1961, was initially observed in normal human fibroblasts that ceased proliferating after a finite number of divisions in culture. This process is triggered by various stimuli, including oxidative stress, chromatin modifications and oncogene activation, characterized by irreversible cell-cycle arrest, resistance to apoptosis and the induction of a complex senescent associated secretory phenotype (SASP). Over the past decade, emerging evidence has linked cellular senescence to the aging process and a wide range of chronic age-related diseases. Consequently, research focused on targeting senescence to alleviate or delay age-related disease, referred to as senotherapy, has been conducted rapidly. Therefore, elucidating the mechanisms of cellular senescence is essential for providing practical strategies aimed at addressing this condition.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2024.1500741</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2024.1500741</link>
        <title><![CDATA[Cellular senescence in acute human infectious disease: a systematic review]]></title>
        <pubdate>2024-11-15T00:00:00Z</pubdate>
        <category>Systematic Review</category>
        <author>William C. Miller</author><author>Stephanie Wallace</author><author>William Kamm</author><author>Erin Reardon</author><author>Nicole Theis-Mahon</author><author>Matthew J. Yousefzadeh</author><author>Elizabeth L. Schmidt</author><author>Laura J. Niedernhofer</author><author>Michael A. Puskarich</author>
        <description><![CDATA[IntroductionAcute infectious disease represents a significant cause of mortality and morbidity in elderly individuals admitted to the hospital. In its extreme, it presents as sepsis, a systematic inflammatory and immunologic response responsible for self-injurious organ injury. As individuals age, a unique set of factors including immunosenescence predispose them to acquiring an infection and a worse clinical prognosis. This systematic review explores the relationship between cellular senescence, an age-related inflammatory phenomenon, with acute human infectious disease.MethodsEmbase via OVID, Scopus, Web of Science, Global Index Medicus, Cochrane Library via Wiley, and ClinicalTrials.gov were queried. Included studies must have compared at least one of the following measures of cellular senescence between patients with an infection and without an infection: cell cycle inhibition measured via levels of p16INK4a and/or p21CIP1, short telomere length, DNA damage via ɣH2AX, high senescence-associated β galactosidase activity, and inflammation via the detection of senescence associated secretory phenotype (SASP). Manuscripts were screened and data collected via two independent reviewers.ResultsA total of 15,828 studies were screened after duplicates were removed. One hundred and fifty-three full-text articles were assessed for eligibility and a total of 16 original articles were included in analysis. Of the 16 original articles included, 12 (75%) articles were centered on SARS-CoV-2, 2 (12.5%) articles utilized patients infected with Leishmania braziliensis, 1 (6.25%) with Plasmodium falciparum, and 1 (6.25%) with Hepatitis C.ConclusionCurrent literature demonstrates robust upregulation of markers of cellular senescence in the setting of acute SARS-CoV-2, P. falciparum, L. braziliensis, and hepatitis C virus, and that markers of senescence correlate with disease severity and persist for months after resolution. Limitations in the number and types of infectious organisms studied, low sample sizes, modest longitudinal sampling, and a lack of consistency in markers measured, the method of measurement, and the definition of normal values represent ongoing gaps in the literature.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421473, Identifier CRD42023421473.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2024.1477528</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2024.1477528</link>
        <title><![CDATA[Persistent elevation of plasma markers of cellular senescence after hip fracture: a pilot longitudinal study]]></title>
        <pubdate>2024-11-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Eric J. Lenze</author><author>Ginger E. Nicol</author><author>George A. Kuchel</author><author>Michael S. Avidan</author><author>Breno S. Diniz</author>
        <description><![CDATA[IntroductionHip fractures may result from and contribute to accelerated biological aging. We aimed to evaluate the impact of hip fracture and its surgery on the senescence-associated secretory phenotype (SASP) index, a composite of peripheral protein markers where higher scores are thought to indicate greater levels of cellular senescence and accelerated aging.MethodsWe examined the SASP index in plasma over 12 weeks post-surgery and its prediction of long-term post-surgical functional outcomes. We included 60 older adults: 20 recruited immediately after hip fracture surgery, and 40 comparison individuals who were either healthy or suffering chronic psychosocial stress (caregiving). We assessed 22 SASP biomarkers and calculated the SASP index score for each hip fracture participant immediately following fracture surgery and 4 and 12 weeks later. Functional recovery was assessed at 12, 26, and 52 weeks after hip replacement surgery.ResultsThe hip fracture group had higher SASP index scores than the comparison groups, after adjusting for potential confounding variables (p = 0.021). SASP index scores in hip fracture patients increased further by week 4 after surgery (p < 0.001), declining by week 12 but remaining elevated overall. However, the SASP index scores were not significantly associated with functional recovery after hip replacement surgery at 26 or 52 weeks after surgery. In conclusion, after hip fracture surgery SASP scores are elevated, continue to rise over time, and do not return to normal by 12 weeks post-surgery.DiscussionOur findings support the need to investigate this phenomenon of post-operative senescence, including whether novel interventions such as senolytics would help older adults facing major surgery.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fragi.2024.1448543</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fragi.2024.1448543</link>
        <title><![CDATA[Systematic transcriptomic analysis and temporal modelling of human fibroblast senescence]]></title>
        <pubdate>2024-08-29T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>R.-L. Scanlan</author><author>L. Pease</author><author>H. O’Keefe</author><author>A. Martinez-Guimera</author><author>L. Rasmussen</author><author>J. Wordsworth</author><author>D. Shanley</author>
        <description><![CDATA[Cellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an associated secretory phenotype (SASP) which includes inflammatory cytokines. Typically, senescent cells are removed by the immune system, but this process becomes dysregulated with age causing senescent cells to accumulate and induce chronic inflammatory signalling. Identifying senescent cells is challenging due to senescence phenotype heterogeneity, and senotherapy often requires a combinatorial approach. Here we systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant variables for each study allowing users to filter for variables and genes of interest. Our own analysis of the database identified 28 genes significantly up- or downregulated across four senescence types (DNA damage induced senescence (DDIS), oncogene induced senescence (OIS), replicative senescence, and bystander induced senescence) compared to proliferating controls. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Our comprehensive data supported several observations made in existing studies using single datasets, including stronger p53 signalling in DDIS compared to OIS. However, contrary to some early observations, both p16 and p21 mRNA levels rise quickly, depending on senescence type, and persist for at least 8–11 days. Additionally, little evidence was found to support an initial TGFβ-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of select core senescence proteins during DDIS and OIS, as well as perform knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a framework for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity.]]></description>
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