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15 pages, 9685 KB

Open AccessArticle

Senescence-Driven Inflammation and Immune Dynamics in the Progression of Radiation Cystitis

by Sabrina Mota, Austin Goodyke, Elijah P. Ward, Rani Mahyoob, Yung-Chun Lee, Sarah N. Bartolone, Alyssa Mularski, Michael B. Chancellor and Bernadette M. M. Zwaans

Cells 2026, 15(4), 337; https://doi.org/10.3390/cells15040337 - 13 Feb 2026

Viewed by 527

Abstract

Pelvic radiation therapy is an essential treatment for several pelvic malignancies, but it can lead to radiation cystitis (RC), a severe progressive inflammatory bladder disorder lacking effective diagnosis and therapeutic options. RC evolves through acute, latent, and chronic phases, ultimately resulting in bladder [...] Read more.

Pelvic radiation therapy is an essential treatment for several pelvic malignancies, but it can lead to radiation cystitis (RC), a severe progressive inflammatory bladder disorder lacking effective diagnosis and therapeutic options. RC evolves through acute, latent, and chronic phases, ultimately resulting in bladder fibrosis, vascular damage, and hematuria. Here, we characterize the molecular and immunological features associated with RC progression using a preclinical mouse model. Building on a prior analysis of the acute and chronic phases, we examined the previously unanalyzed latent phase and integrated transcriptomics, immune cell profiling, inflammatory protein measurements, and bladder function assessments across all stages. Acute radiation injury was marked by the strong activation of apoptotic pathways, whereas latent and chronic phases were dominated by inflammatory signaling with distinct cytokine and chemokine signatures. The persistent upregulation of Cdkn1a (P21) was consistent with sustained senescence-associated signaling, while reductions in IL-27 and shifts in the granulocyte–lymphocyte-enriched immune population during the latent phase were consistent with altered immune regulatory states. At chronic stages, increased SASP-associated proteins and matrix remodeling mediators coincided with bladder functional decline. Together, these findings support a model in which radiation-induced senescence, coupled with immune dysregulation during the latent phase, are coordinated features accompanying inflammation, tissue remodeling, and bladder dysfunction in RC. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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16 pages, 2072 KB

Open AccessArticle

Loss of HuD Sensitizes Neuroblastoma Cells to Palmitate-Driven Stress-Induced Premature Senescence via PPARα Downregulation and FAO Impairment

by Seungyeon Ryu, Jiyoon Seo, Ye Eun Sim, Se Hoon Jung, Wei Zhang, Seung Min Jeong and Eun Kyung Lee

Cells 2026, 15(4), 316; https://doi.org/10.3390/cells15040316 - 7 Feb 2026

Viewed by 881

Abstract

Metabolic stress caused by lipid overload is a key driver of cellular dysfunction in aging and disease. Excess saturated fatty acids such as palmitate impair fatty acid oxidation (FAO), promote lipid accumulation, and increase reactive oxygen species (ROS), ultimately triggering premature senescence-like states. [...] Read more.

Metabolic stress caused by lipid overload is a key driver of cellular dysfunction in aging and disease. Excess saturated fatty acids such as palmitate impair fatty acid oxidation (FAO), promote lipid accumulation, and increase reactive oxygen species (ROS), ultimately triggering premature senescence-like states. Senescence further amplifies vulnerability by worsening mitochondrial dysfunction, enhancing lipid imbalance, and sustaining pro-inflammatory signaling. Here, we investigated the role of the neuron-enriched RNA-binding protein HuD (ELAVL4) in protecting cells against lipotoxic stress. Using Neuro2a neuroblastoma cells, we found that HuD knockdown suppressed FAO, leading to increased lipid accumulation and elevated ROS following palmitate exposure. HuD-deficient cells also exhibited cytosolic mitochondrial DNA release, IRF phosphorylation, and upregulation of senescence markers. Mechanistically, RNA immunoprecipitation revealed that HuD binds directly to PPARα mRNA, sustaining its expression by competing with the PPARα-targeting microRNAs miR-9-5p and miR-22-3p. Loss of HuD reduced PPARα levels, thereby weakening the FAO capacity and sensitizing cells to palmitate-induced lipotoxic stress. These findings identify a previously unrecognized HuD–PPARα–FAO axis that restrains metabolic stress and senescence. By linking post-transcriptional regulation to lipid metabolism and inflammatory signaling, this work highlights stress-induced premature senescence as both an outcome and a propagator of metabolic dysfunction, providing insight into mechanisms of aging-related vulnerability. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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15 pages, 6719 KB

Open AccessArticle

circSATB1 Modulates Cell Senescence in Age-Related Acute Myeloid Leukemia: A Mechanistic Proposal

by Linxiang Han, Xi Wen, Ling Zhang, Xingcheng Yang, Ziyan Wei, Haodong Wu, Yichen Zhan, Huiting Wang and Yu Fang

Cells 2025, 14(15), 1181; https://doi.org/10.3390/cells14151181 - 31 Jul 2025

Viewed by 1161

Abstract

Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated [...] Read more.

Acute myeloid leukemia (AML) is a malignant hematological tumor with a high prevalence in elderly people, and circular RNA (circRNA) plays an important role in age-related diseases. Induction of cancer cell senescence is a highly promising therapeutic strategy; however, the presence of senescence-associated circRNAs in AML remains to be elucidated. Here, we show that the expression patterns of circRNAs differed between elderly AML patients and healthy volunteers. circSATB1 was significantly overexpressed in elderly patients and AML cells. Knockdown of circSATB1 resulted in the inhibition of proliferation and arrest of the cell cycle in the G0/G1 phase; no effect on apoptosis or DNA integrity was observed, and precocious cellular senescence was promoted, characterized by no change in telomere length. Database analysis revealed that there may be two miRNA and nine RNA-binding proteins (RBPs) involved in regulating the cellular functions of circSATB1. Our observations uncover circSATB1-orchestrated cell senescence in AML, which provides clues for finding more modest therapeutic targets for AML. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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12 pages, 1574 KB

Open AccessArticle

Genome Instability and Senescence Are Markers of Cornelia de Lange Syndrome Cells

by Maddalena Di Nardo, Ian D. Krantz and Antonio Musio

Cells 2024, 13(23), 2025; https://doi.org/10.3390/cells13232025 - 7 Dec 2024

Cited by 2 | Viewed by 2697

Abstract

Cornelia de Lange syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder. Pathogenic variants in genes encoding the structural subunits and regulatory proteins of the cohesin complex (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the primary [...] Read more.

Cornelia de Lange syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder. Pathogenic variants in genes encoding the structural subunits and regulatory proteins of the cohesin complex (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the primary contributors to the pathogenesis of CdLS. Pathogenic variations in these genes disrupt normal cohesin function, leading to the syndrome’s diverse and complex clinical presentation. In this study, we discovered that cells harboring variants in the NIPBL, SMC1A and HDAC8 genes exhibit spontaneous genome instability, elevated oxidative stress and premature cellular aging. These findings suggest that cohesin plays a critical role in maintaining proper cellular function and highlight its contribution to the pathophysiology seen in the related diagnoses. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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21 pages, 8084 KB

Open AccessArticle

Stimuli-Specific Senescence of Primary Human Lung Fibroblasts Modulates Alveolar Stem Cell Function

by Maria Camila Melo-Narváez, Nora Bramey, Fenja See, Katharina Heinzelmann, Beatriz Ballester, Carina Steinchen, Eshita Jain, Kathrin Federl, Qianjiang Hu, Deepesh Dhakad, Jürgen Behr, Oliver Eickelberg, Ali Önder Yildirim, Melanie Königshoff and Mareike Lehmann

Cells 2024, 13(13), 1129; https://doi.org/10.3390/cells13131129 - 29 Jun 2024

Cited by 11 | Viewed by 5417

Abstract

Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging like cellular senescence are increased in these patients in different lung cell types including fibroblasts. However, little [...] Read more.

Aging is the main risk factor for chronic lung diseases (CLDs) including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Accordingly, hallmarks of aging like cellular senescence are increased in these patients in different lung cell types including fibroblasts. However, little is known about the different triggers that induce a senescence phenotype in different disease backgrounds and its role in CLD pathogenesis. Therefore, we characterized senescence in primary human lung fibroblasts (phLF) from control, IPF, or COPD patients at baseline and after exposure to disease-relevant insults (H₂O₂, bleomycin, TGF-β1) and studied their capacity to support progenitor cell potential in a lung organoid model. Bulk-RNA sequencing revealed that phLF from IPF and COPD activate different transcriptional programs but share a similar senescence phenotype at baseline. Moreover, H₂O₂ and bleomycin but not TGF-β1 induced senescence in phLF from different disease origins. Exposure to different triggers resulted in distinct senescence programs in phLF characterized by different SASP profiles. Finally, co-culture with bleomycin- and H₂O₂-treated phLF reduced the progenitor cell potential of alveolar epithelial progenitor cells. In conclusion, phLF from COPD and IPF share a conserved senescence response that varies depending on the insult and impairs alveolar epithelial progenitor capacity ex vivo. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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22 pages, 5875 KB

Open AccessArticle

In Vitro Investigation of Therapy-Induced Senescence and Senescence Escape in Breast Cancer Cells Using Novel Flow Cytometry-Based Methods

by Fanni Tóth, Zahra Moftakhar, Federica Sotgia and Michael P. Lisanti

Cells 2024, 13(10), 841; https://doi.org/10.3390/cells13100841 - 15 May 2024

Cited by 12 | Viewed by 5137

Abstract

Although cellular senescence was originally defined as an irreversible form of cell cycle arrest, in therapy-induced senescence models, the emergence of proliferative senescence-escaped cancer cells has been reported by several groups, challenging the definition of senescence. Indeed, senescence-escaped cancer cells may contribute to [...] Read more.

Although cellular senescence was originally defined as an irreversible form of cell cycle arrest, in therapy-induced senescence models, the emergence of proliferative senescence-escaped cancer cells has been reported by several groups, challenging the definition of senescence. Indeed, senescence-escaped cancer cells may contribute to resistance to cancer treatment. Here, to study senescence escape and isolate senescence-escaped cells, we developed novel flow cytometry-based methods using the proliferation marker Ki-67 and CellTrace CFSE live-staining. We investigated the role of a novel senescence marker (DPP4/CD26) and a senolytic drug (azithromycin) on the senescence-escaping ability of MCF-7 and MDA-MB-231 breast cancer cells. Our results show that the expression of DPP4/CD26 is significantly increased in both senescent MCF-7 and MDA-MB-231 cells. While not essential for senescence induction, DPP4/CD26 contributed to promoting senescence escape in MCF-7 cells but not in MDA-MB-231 cells. Our results also confirmed the potential senolytic effect of azithromycin in senescent cancer cells. Importantly, the combination of azithromycin and a DPP4 inhibitor (sitagliptin) demonstrated a synergistic effect in senescent MCF-7 cells and reduced the number of senescence-escaped cells. Although further research is needed, our results and novel methods could contribute to the investigation of the mechanisms of senescence escape and the identification of potential therapeutic targets. Indeed, DPP4/CD26 could be a promising marker and a novel target to potentially decrease senescence escape in cancer. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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19 pages, 5885 KB

Open AccessArticle

GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts

by Ann Nitzsche, Christoph-Ludwig Hennig, Katrin von Brandenstein, Annika Döding, Ulrike Schulze-Späte, Judit Symmank and Collin Jacobs

Cells 2024, 13(2), 147; https://doi.org/10.3390/cells13020147 - 12 Jan 2024

Cited by 6 | Viewed by 3365

Abstract

Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal ligament (PdL), a connecting tissue between the alveolar bone and teeth. PdL cells, mainly fibroblasts (PdLFs), are crucial regulators [...] Read more.

Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal ligament (PdL), a connecting tissue between the alveolar bone and teeth. PdL cells, mainly fibroblasts (PdLFs), are crucial regulators in OTM by modulating force-induced local inflammatory processes. Recently, we identified the TGF-β/BMP superfamily member GDF15 as an important modulator in OTM, promoting the pro-inflammatory mechanoresponses of PdLFs. The precise impact of the highly potent BP zoledronate (ZOL) on the mechanofunctionality of PdLFs is still under-investigated. Therefore, the aim of this study was to further characterize the ZOL-induced changes in the initial inflammatory mechanoresponse of human PdLFs (hPdLFs) and to further clarify a potential interrelationship with GDF15 signaling. Thus, two-day in vitro treatment with 0.5 µM, 5 µM and 50 µM of ZOL altered the cellular properties of hPdLFs partially in a concentration-dependent manner. In particular, exposure to ZOL decreased their metabolic activity, the proliferation rate, detected using Ki-67 immunofluorescent staining, and survival, analyzed using trypan blue. An increasing occurrence of DNA strand breaks was observed using TUNEL and an activated DNA damage response was demonstrated using H2A.X (phosphoS139) staining. While the osteogenic differentiation of hPdLFs was unaffected by ZOL, increased cellular senescence was observed using enhanced p21^{Waf1/Cip1/Sdi1} and β-galactosidase staining. In addition, cytokine-encoding genes such as IL6, IL8, COX2 and GDF15, which are associated with a senescence-associated secretory phenotype, were up-regulated by ZOL. Subsequently, this change in the hPdLF phenotype promoted a hyperinflammatory response to applied compressive forces with an increased expression of the pro-inflammatory markers IL1β, IL6 and GDF15, as well as the activation of monocytic THP1 cells. GDF15 appeared to be particularly relevant to these changes, as siRNA-mediated down-regulation balanced these hyperinflammatory responses by reducing IL-1β and IL-6 expression (IL1B p-value < 0.0001; IL6 p-value < 0.001) and secretion (IL-1β p-value < 0.05; IL-6 p-value < 0.001), as well as immune cell activation (p-value < 0.0001). In addition, ZOL-related reduced RANKL/OPG values and inhibited osteoclast activation were enhanced in GDF15-deficient hPdLFs (both p-values < 0.0001; all statistical tests: one-way ANOVA, Tukey’s post hoc test). Thus, GDF15 may become a promising new target in the personalized orthodontic treatment of bisphosphonatepatients. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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Review

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29 pages, 1226 KB

Open AccessReview

Plasminogen Activator Inhibitor 1, Cell Senescence, and Aging-Related Diseases

by Rui-Ming Liu and Mary F. Nakamya

Cells 2026, 15(6), 551; https://doi.org/10.3390/cells15060551 - 19 Mar 2026

Viewed by 811

Abstract

Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), is a state of the permanent arrest of cell growth, which can occur in proliferative cells and post-mitotic cells. Cellular senescence is believed to contribute importantly to aging and aging-related diseases. Although [...] Read more.

Cellular senescence, including replicative senescence (RS) and stress-induced premature senescence (SIPS), is a state of the permanent arrest of cell growth, which can occur in proliferative cells and post-mitotic cells. Cellular senescence is believed to contribute importantly to aging and aging-related diseases. Although several hypotheses, including telomere shortening, oncogene activation, oxidative stress, DNA damage, and mitochondrial dysfunction, have been proposed, the mechanisms underlying cellular senescence in either physiological or pathological conditions remain poorly understood. Plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tissue type and urokinase type of plasminogen activators (tPA and uPA), has multiple functions. PAI-1 expression increases with age and in many aging-related diseases. Importantly, increased PAI-1 expression is not only a marker but also a mediator of cell senescence induced by different stimuli in vitro and in vivo. This review focuses on the recent advance in the role of PAI-1 in cell senescence during aging and in aging-related diseases as well as the potential mechanisms by which PAI-1 promotes cell senescence. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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23 pages, 2157 KB

Open AccessReview

Immune Ageing Clocks: A Methods-Oriented Review of Tasks, Modalities, Models, and Recalibration

by Gengchen Yu, Zeyu Shao, Jingyu Zhuo and Zixuan Chen

Cells 2026, 15(5), 421; https://doi.org/10.3390/cells15050421 - 27 Feb 2026

Viewed by 772

Abstract

Population ageing and the growing burden of immune-mediated disease have prompted efforts to quantify immunosenescence with clinically usable biomarkers. Immune ageing clocks have been built from immunophenotyping, transcriptomics, proteomics, epigenomics and adaptive receptor repertoires, but heterogeneous task definitions, assay protocols and evaluation criteria [...] Read more.

Population ageing and the growing burden of immune-mediated disease have prompted efforts to quantify immunosenescence with clinically usable biomarkers. Immune ageing clocks have been built from immunophenotyping, transcriptomics, proteomics, epigenomics and adaptive receptor repertoires, but heterogeneous task definitions, assay protocols and evaluation criteria limit comparability and translation. We review major immune data modalities and outline an end-to-end workflow from cohort design and assay standardisation to preprocessing, feature engineering, model development, validation and recalibration. We propose a task–modality–model taxonomy separating (i) chronological age clocks, (ii) outcome-anchored risk clocks and (iii) cell lineage/state clocks, while treating bulk blood transcriptomics (whole blood or PBMC) as a molecular-layer modality that can support either age-scale or outcome-anchored tasks depending on supervision. Across studies, common limitations include batch effects, compositional confounding, endpoint mismatch, scarce external validation and limited mechanistic anchoring. We conclude with priorities for the field, including multimodal integration, longitudinal designs with digital phenotypes, tissue- and cell-type-specific models, and pathway-grounded clocks that can be linked to interventions. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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23 pages, 1045 KB

Open AccessReview

From Senescent Cells to Systemic Inflammation: The Role of Inflammaging in Age-Related Diseases and Kidney Dysfunction

by Federica De Luca, Valentina Camporeale, Giorgia Leccese, Roberto Cuttano, Dario Troise, Barbara Infante, Giovanni Stallone, Giuseppe Stefano Netti and Elena Ranieri

Cells 2025, 14(22), 1831; https://doi.org/10.3390/cells14221831 - 20 Nov 2025

Cited by 4 | Viewed by 2817

Abstract

Aging is characterized by a chronic, low-grade inflammatory state known as inflammaging, which closely interacts with immunosenescence—the gradual deterioration of immune function. Together, these processes contribute to tissue dysfunction and the development of age-related diseases. This review explores the cellular and molecular mechanisms [...] Read more.

Aging is characterized by a chronic, low-grade inflammatory state known as inflammaging, which closely interacts with immunosenescence—the gradual deterioration of immune function. Together, these processes contribute to tissue dysfunction and the development of age-related diseases. This review explores the cellular and molecular mechanisms underlying inflammaging, including mitochondrial dysfunction, telomere attrition, impaired autophagy, and gut microbiota dysbiosis. A particular emphasis is given to the senescence-associated secretory phenotype (SASP), which sustains a pro-inflammatory microenvironment and exacerbates tissue damage. We further discuss the impact of inflammaging on major age-related pathologies, with a focus on the kidney as a paradigmatic model of age-related decline, where inflammaging and cellular senescence contribute to chronic kidney disease (CKD) and impaired regeneration. Finally, we summarize emerging therapeutic strategies such as senolytics, senomorphics, immunomodulation, and lifestyle interventions, aimed at reducing the burden of senescent cells, mitigating inflammaging and extending healthspan. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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17 pages, 1930 KB

Open AccessReview

Role of the Interplay Between Autophagy and Cell Senescence in the Pathogenesis and Therapeutics of Glioblastoma in the Aging Population

by Eliezer Masliah

Cells 2025, 14(22), 1764; https://doi.org/10.3390/cells14221764 - 11 Nov 2025

Viewed by 1184

Abstract

Glioblastoma (GBM), formerly referred to as glioblastoma multiforme, represents the most prevalent and aggressive form of glioma, predominantly affecting the aging population. Despite considerable advances in recent years in elucidating its pathogenesis and developing novel immunotherapeutic approaches, the overall survival rate for patients [...] Read more.

Glioblastoma (GBM), formerly referred to as glioblastoma multiforme, represents the most prevalent and aggressive form of glioma, predominantly affecting the aging population. Despite considerable advances in recent years in elucidating its pathogenesis and developing novel immunotherapeutic approaches, the overall survival rate for patients with this central nervous system (CNS) neoplasm remains dismally low. Consequently, there is an urgent and unmet need to identify and characterize additional therapeutic targets that could be employed synergistically with existing treatment modalities to enhance both survival outcomes and quality of life. Among the emerging areas of investigation, substantial interest has been directed toward aging-associated molecular signaling mechanisms that also constitute key oncogenic pathways in GBM. These include aberrant growth factor signaling, hyperactivation of the PI3K/AKT/mTOR axis, and inactivation of critical tumor suppressor pathways such as p53 and retinoblastoma (RB). The dysregulation of these signaling cascades results in profound disturbances of essential cellular homeostatic processes, notably autophagy and cellular senescence, which are intimately involved in both tumor initiation and progression. This review aims to delineate the complex interplay between autophagy and cellular senescence within the context of aging-related GBM pathogenesis. Furthermore, it explores the relevant intracellular signaling transduction mechanisms that govern these processes and discusses prospective therapeutic strategies. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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27 pages, 2781 KB

Open AccessReview

p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer

by Lakshana Sruthi Sadu Murari, Sam Kunkel, Anala Shetty, Addison Bents, Aayush Bhandary and Juan Carlos Rivera-Mulia

Cells 2025, 14(1), 43; https://doi.org/10.3390/cells14010043 - 3 Jan 2025

Cited by 3 | Viewed by 6501

Abstract

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out [...] Read more.

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases. miRNA-p63 interactions are also critical regulators in the context of cancer metastasis. This review aims to elaborate on the diverse roles of p63, focusing on disease, development, and the mechanisms controlling genome organization and function. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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23 pages, 1210 KB

Open AccessReview

The Hippo Signaling Pathway Manipulates Cellular Senescence

by Chiharu Miyajima, Mai Nagasaka, Hiromasa Aoki, Kohki Toriuchi, Shogo Yamanaka, Sakura Hashiguchi, Daisuke Morishita, Mineyoshi Aoyama, Hidetoshi Hayashi and Yasumichi Inoue

Cells 2025, 14(1), 13; https://doi.org/10.3390/cells14010013 - 26 Dec 2024

Cited by 4 | Viewed by 4955

Abstract

The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant [...] Read more.

The Hippo pathway, a kinase cascade, coordinates with many intracellular signals and mediates the regulation of the activities of various downstream transcription factors and their coactivators to maintain homeostasis. Therefore, the aberrant activation of the Hippo pathway and its associated molecules imposes significant stress on tissues and cells, leading to cancer, immune disorders, and a number of diseases. Cellular senescence, the mechanism by which cells counteract stress, prevents cells from unnecessary damage and leads to sustained cell cycle arrest. It acts as a powerful defense mechanism against normal organ development and aging-related diseases. On the other hand, the accumulation of senescent cells without their proper removal contributes to the development or worsening of cancer and age-related diseases. A correlation was recently reported between the Hippo pathway and cellular senescence, which preserves tissue homeostasis. This review is the first to describe the close relationship between aging and the Hippo pathway, and provides insights into the mechanisms of aging and the development of age-related diseases. In addition, it describes advanced findings that may lead to the development of tissue regeneration therapies and drugs targeting rejuvenation. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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18 pages, 973 KB

Open AccessReview

New Possibilities for Evaluating the Development of Age-Related Pathologies Using the Dynamical Network Biomarkers Theory

by Kazutaka Akagi, Keiichi Koizumi, Makoto Kadowaki, Isao Kitajima and Shigeru Saito

Cells 2023, 12(18), 2297; https://doi.org/10.3390/cells12182297 - 17 Sep 2023

Cited by 5 | Viewed by 3497

Abstract

Aging is the slowest process in a living organism. During this process, mortality rate increases exponentially due to the accumulation of damage at the cellular level. Cellular senescence is a well-established hallmark of aging, as well as a promising target for preventing aging [...] Read more.

Aging is the slowest process in a living organism. During this process, mortality rate increases exponentially due to the accumulation of damage at the cellular level. Cellular senescence is a well-established hallmark of aging, as well as a promising target for preventing aging and age-related diseases. However, mapping the senescent cells in tissues is extremely challenging, as their low abundance, lack of specific markers, and variability arise from heterogeneity. Hence, methodologies for identifying or predicting the development of senescent cells are necessary for achieving healthy aging. A new wave of bioinformatic methodologies based on mathematics/physics theories have been proposed to be applied to aging biology, which is altering the way we approach our understand of aging. Here, we discuss the dynamical network biomarkers (DNB) theory, which allows for the prediction of state transition in complex systems such as living organisms, as well as usage of Raman spectroscopy that offers a non-invasive and label-free imaging, and provide a perspective on potential applications for the study of aging. Full article

(This article belongs to the Special Issue The Role of Cellular Senescence in Health, Disease, and Aging)

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