Review
Oncology
Chen Wang, Xue Hao, Rugang Zhang
Summary: This review summarizes the role of cellular senescence in aging and age-related diseases such as cancer. The authors discuss current strategies for targeting senescence in order to develop therapeutic interventions for cancer and promote healthy aging, and outline future research directions for senescence-based interventions.
MOLECULAR ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Helene Martini, Joao F. Passos
Summary: The article discusses how the accumulation of senescent cells in multiple tissues leads to tissue dysfunction and age-related diseases, and emphasizes the important role and mechanisms of mitochondria in senescence. It also proposes the establishment of a detailed road map of mitochondrial biology to guide future research on treatments.
Review
Cell Biology
Evon Low, Ghazaleh Alimohammadiha, Lucy A. Smith, Lydia F. Costello, Stefan A. Przyborski, Thomas von Zglinicki, Satomi Miwa
Summary: Skin, as the largest organ of the body, is compromised with time due to intrinsic and extrinsic ageing processes, primarily at the cellular level through cellular senescence. While evidence suggests that cellular senescence is a relevant cause of intrinsic skin ageing, it is not yet completely conclusive.
AGEING RESEARCH REVIEWS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Darren J. Baker, Masashi Narita, Pura Munoz-Canoves
Summary: The contribution of cellular senescence in various biological processes has been overlooked but is now gaining attention. This Editorial provides an overview of the review and original work articles in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. Senescent cells have both positive and negative effects on tissue injury, aging, and pathology. The identification of senescent cells has improved, especially in slow-proliferating or terminally differentiated tissues. The communication between senescent cells and other tissue residents, as well as the role of the senescence-associated secretory phenotype (SASP), are important topics in this Special Issue.
Article
Biochemistry & Molecular Biology
Estela Gonzalez-Gualda, Andrew G. Baker, Ljiljana Fruk, Daniel Munoz-Espin
Summary: Cellular senescence is a physiological mechanism with beneficial roles in physiology, but can also have antagonistic effects in diseases and cancer. Despite the establishment of a general set of hallmarks describing senescence, complexities such as phenotype heterogeneity have made recognition and evaluation challenging.
Review
Biochemistry & Molecular Biology
Victoria Moiseeva, Andres Cisneros, Aina Calls Cobos, Aida Bea Tarrega, Claudia Santos Onate, Eusebio Perdiguero, Antonio L. Serrano, Pura Munoz-Canoves
Summary: Cellular senescence is an irreversible cell cycle arrest state that occurs after tissue damage and in age-related diseases. Senescent cells and their multicomponent secretory phenotype (SASP) can impact tissue regeneration and function, but the effects vary depending on the tissue environment, duration of injury, persistence of senescent cells, and organism's age. Transient presence of senescent cells is believed to be beneficial for tissue regeneration, but recent data suggest it is harmful after acute damage, while persistent presence of senescent cells is typically associated with the progression of age-related chronic degenerative diseases, yet it appears to be necessary for correct tissue function in the elderly.
Article
Geriatrics & Gerontology
Miles D. Witham, Antoneta Granic, Satomi Miwa, Joao F. Passos, Gavin D. Richardson, Avan A. Sayer
Summary: Cellular senescence is a fundamental biological mechanism contributing to aging and age-related diseases. It can be induced by various mechanisms, not just replication and telomere attrition. Senescent cells secrete inflammatory mediators that drive chronic inflammation and can convert other cells to the senescent state. Research in animal models suggests that preventing or reversing senescence may be a potential strategy against aging and age-related diseases, with interventions including exercise, nutrition, and senolytics/senostatic drugs. However, it is crucial to measure outcomes reflecting improved healthy life expectancy in clinical studies to gain trust from clinicians, patients, and the public.
Review
Oncology
Andreas Domen, Christophe Deben, Jasper Verswyvel, Tal Flieswasser, Hans Prenen, Marc Peeters, Filip Lardon, An Wouters
Summary: Cellular senescence is a mechanism in which cells enter a state of stable cell-cycle arrest with secretory features in response to cellular stress. It has been historically seen as a protective mechanism against cancer by eliminating damaged cells. However, the accumulation of senescent cells can have long-term detrimental effects and contribute to age-related diseases, including cancer. The role of cellular senescence in cancer is ambiguous and controversial, and its detection and study in cancer patients present challenges. This review highlights the methods and challenges of detecting cellular senescence in cancer patients, and discusses its prognostic implications.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Cell Biology
Jing Yang, Mengmeng Liu, Dongchun Hong, Musheng Zeng, Xing Zhang
Summary: Cellular senescence in cancer presents a dual role, acting as both a preventative measure and a promoter of tumor development. Senescent cells contribute to oncogenesis through their secretory phenotype, both inhibiting tumor growth and creating an environment conducive to tumor progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jaskaren Kohli, Iris Veenstra, Marco Demaria
Summary: Cellular senescence is a stable cell cycle arrest associated with macromolecular alterations and inflammation, which play important roles in controlling viral spread and activating immune responses. However, excessive and aberrant senescent cells can lead to pathology and dysfunction. Pharmacological interventions, including antiviral therapies, can induce premature senescence and have detrimental effects if not controlled properly.
Review
Biochemistry & Molecular Biology
Lorna W. Harries
Summary: The human genome produces a wide range of proteins and non-coding RNAs through the coordinated processes of mRNA processing and metabolism. Dysfunctional RNA processing and metabolism have been implicated in cellular senescence and may be a key contributor to aging.
Review
Biochemistry & Molecular Biology
Maria Elzbieta Mycielska, Emma Naomi James, Eric Kenneth Parkinson
Summary: Recent experiments in mouse models have shown that senescent cells play a crucial role in age-related diseases and may contribute to certain pathological conditions. The recognition of extranuclear chromatin by the cyclic GMP-AMP synthase-stimulator of interferon genes pathway leads to the induction of inflammatory cytokines, which are part of the senescence-associated secretory phenotype. This chronic inflammation increases with age and age-related diseases. In addition, senescent cells undergo metabolic changes, including the accumulation of extracellular citrate, which may also contribute to age-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Anna Grigorevna Sorokina, Yana Arturovna Orlova, Olga Aleksandrovna Grigorieva, Ekaterina Sergeevna Novoseletskaya, Nataliya Andreevna Basalova, Natalya Andreevna Alexandrushkina, Maksim Aleksandrovich Vigovskiy, Karina Igorevna Kirillova, Alexander Vladimirovich Balatsky, Larisa Mihailovna Samokhodskaya, Natalya Vladimirovna Danilova, Uliana Denisovna Dyachkova, Victor Victorovich Kakotkin, David Albertovich Asratyan, Zhanna Alekseevna Akopyan, Anastasia Yurievna Efimenko
Summary: The aim of this study was to explore the relationship between established clinical biomarkers of aging and the development of age-related diseases and senescent cell biomarkers at tissue and cellular levels. The findings confirmed a significant correlation between tissue p16 expression and age, pulse wave velocity, vascular cell adhesion molecule (VCAM-1) content in the systemic blood stream, as well as p16 mRNA level in blood mononuclear cells (MNCs). The proliferation indicators of fibroblasts (FBs) and mesenchymal stem/stromal cells (MSCs) in culture showed significant correlations with the acquisition of senescence-associated secretory phenotype (SASP) by the cells.
EXPERIMENTAL GERONTOLOGY
(2023)
Review
Cell Biology
Dilara Demirci, Bengisu Dayanc, Fatma Aybuke Mazi, Serif Senturk
Summary: Cellular senescence is a state of stable cell cycle arrest triggered by various insults, with potential adverse implications such as inflammation, cancer stemness, senescence reversal, therapy resistance, and disease recurrence, which can be mitigated by eliminating senescent cells or inhibiting their SASP production to enhance cancer therapy efficacy.
Article
Biochemistry & Molecular Biology
Samprikta Manna, Colm J. J. Mc Elwain, Gillian M. M. Maher, Marta Giralt Martin, Andrea Musumeci, Fergus P. P. McCarthy, Cathal McCarthy
Summary: This study investigated the cellular senescence phenotypes of pre-eclampsia and intrauterine growth restriction (IUGR) pregnancies by measuring multiple biomarkers of senescence. The results showed signs of premature senescence in IUGR pregnancies, while pre-eclampsia activated cell cycle checkpoint regulators but with a phenotype of cell repair and proliferation rather than senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Developmental Biology
Naoki Takada, Masaki Takasugi, Yoshiki Nonaka, Tomonori Kamiya, Kazuaki Takemura, Junko Satoh, Shinji Ito, Kosuke Fujimoto, Satoshi Uematsu, Kayo Yoshida, Takashi Morita, Hiroaki Nakamura, Akiyoshi Uezumi, Naoko Ohtani
Summary: The worldwide prevalence of obesity is connected to lifestyle-related diseases. This study investigated the processes underlying the formation of intermuscular adipose tissue (IMAT) in obese mice and identified a small population of PDGFR alpha(+) cells that were strongly directed towards adipogenesis. The increase in galectin-3 in the interstitial environments was found to activate adipogenic signals, while the knockout of galectin-3 significantly suppressed IMAT formation during muscle regeneration. These findings provide insights into the microenvironmental networks during muscle regeneration and highlight potential therapeutic targets for IMAT formation in obesity.
Article
Biochemistry & Molecular Biology
Boshi Wang, Marta Varela-Eirin, Simone M. Brandenburg, Alejandra Hernandez-Segura, Thijmen van Vliet, Elisabeth M. Jongbloed, Saskia M. Wilting, Naoko Ohtani, Agnes Jager, Marco Demaria
Summary: Cellular senescence is a state of stable growth arrest that is desired in tumor suppressive interventions. Treatment with anti-cancer drugs can cause premature senescence of non-malignant cells. However, exposure to CDK4/6 inhibitors induces a senescence-like program in non-malignant cells without the negative effects observed in therapy-induced senescent cells.
Review
Biochemistry & Molecular Biology
Masaki Takasugi, Yuya Yoshida, Eiji Hara, Naoko Ohtani
Summary: Cellular senescence is an irreversible cell cycle arrest induced by various stresses, playing a crucial role in tumor suppression. The altered secretory profile of senescent cells contributes to the microenvironment promoting tumor development. Understanding the mechanisms underlying the diversity of the senescence-associated secretory phenotype allows the development of strategies to target senescent cells for cancer therapy effectively.
Review
Cell Biology
Kenichi Miyata, Akiko Takahashi
Summary: Cellular senescence leads to significant changes in chromatin organization and gene expression profile, contributing to age-related pathologies and potentially promoting malignant transformation through the senescence-associated secretory phenotype (SASP).
Article
Multidisciplinary Sciences
Nanase Igarashi, Kenichi Miyata, Tze Mun Loo, Masatomo Chiba, Aki Hanyu, Mika Nishio, Hiroko Kawasaki, Hao Zheng, Shinya Toyokuni, Shunsuke Kon, Keiji Moriyama, Yasuyuki Fujita, Akiko Takahashi
Summary: Cellular senescence inhibits the elimination of oncogenic cells through HGF signaling, suggesting its role in cancer development during aging.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Ryota Yamagishi, Fumitaka Kamachi, Masaru Nakamura, Shota Yamazaki, Tomonori Kamiya, Masaki Takasugi, Yi Cheng, Yoshiki Nonaka, Yoshimi Yukawa-Muto, Le Thi Thanh Thuy, Yohsuke Harada, Tatsuya Arai, Tze Mun Loo, Shin Yoshimoto, Tatsuya Ando, Masahiro Nakajima, Hayao Taguchi, Takamasa Ishikawa, Hisaya Akiba, Sachiko Miyake, Masato Kubo, Yoichiro Iwakura, Shinji Fukuda, Wei-Yu Chen, Norifumi Kawada, Alexander Rudensky, Susumu Nakae, Eiji Hara, Naoko Ohtani
Summary: In this study, the release mechanism of senescence-associated secretory phenotype (SASP) factors from senescent hepatic stellate cells (HSCs) was identified in a mouse model of obesity-induced hepatocellular carcinoma (HCC). IL-33 release from HSCs promoted HCC development via the activation of ST2-positive T-reg cells in the liver tumor microenvironment. These findings highlight the therapeutic potential of inhibitors of gasdermin D-mediated pore formation for HCC treatment.
SCIENCE IMMUNOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Yi Cheng, Ryota Yamagishi, Yoshiki Nonaka, Misako Sato-Matsubara, Norifumi Kawada, Naoko Ohtani
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Truong Huu Hoang, Misako Sato-Matsubara, Hideto Yuasa, Tsutomu Matsubara, Le Thi Thanh Thuy, Hiroko Ikenaga, Dong Minh Phuong, Ngo Vinh Hanh, Vu Ngoc Hieu, Dinh Viet Hoang, Hoang Hai, Yoshinori Okina, Masaru Enomoto, Akihiro Tamori, Atsuko Daikoku, Hayato Urushima, Kazuo Ikeda, Ninh Quoc Dat, Yutaka Yasui, Hiroji Shinkawa, Shoji Kubo, Ryota Yamagishi, Naoko Ohtani, Katsutoshi Yoshizato, Jordi Gracia-Sancho, Norifumi Kawada
Summary: This study discovered that cancer cells induce intracellular gap formation in liver sinusoidal endothelial cells (LSECs) through proinflammatory paracrine mechanisms, and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver.
Article
Biochemistry & Molecular Biology
Tomoka Misawa, Kazuhiro Hitomi, Kenichi Miyata, Yoko Tanaka, Risa Fujii, Masatomo Chiba, Tze Mun Loo, Aki Hanyu, Hiroko Kawasaki, Hisaya Kato, Yoshiro Maezawa, Koutaro Yokote, Asako J. Nakamura, Koji Ueda, Nobuo Yaegashi, Akiko Takahashi
Summary: Senescent cells exhibit a secretory phenotype that promotes inflammation and age-related diseases. This study identified ATP6V0D1 and RTN4 as novel markers upregulated in small extracellular vesicles (sEVs) from senescent cells and aged mice, suggesting their potential use for detecting senescent cells in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Masaki Takasugi, Yuya Yoshida, Yoshiki Nonaka, Naoko Ohtani
Summary: Despite comprehensive transcriptome analyses, the actual impact of transcriptome on aging and species maximum lifespan (MLS) has remained elusive. However, our study found significant similarities between transcriptomic signatures associated with mammalian MLS and aging, suggesting that gene expression patterns associated with MLS contribute to extended lifespan within and across species. Furthermore, we identified evidence of co-evolution between MLS and promoter sequences of MLS-associated genes, highlighting the evolutionary contribution of specific transcription factor binding motifs in shaping MLS-associated gene expression signature. This study emphasizes the importance of considering the adaptive aspects of aging transcriptome and demonstrates the power of cross-species genomics in understanding adaptive aging transcriptome.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Gastroenterology & Hepatology
Naoko Ohtani, Tomonori Kamiya, Norifumi Kawada
Summary: The gut and the liver are connected through the gut-liver axis, which influences liver physiology and pathology. The gut microbiota triggers innate immunity and affects the liver immune microenvironment. It also influences metabolism and the efficacy of immunotherapy in liver diseases.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Masatomo Chiba, Kenichi Miyata, Hikaru Okawa, Yoko Tanaka, Koji Ueda, Hiroyuki Seimiya, Akiko Takahashi
Summary: Senescent cells secrete inflammatory proteins and sEVs, which contribute to age-related diseases. This study reveals that YBX1 is involved in loading SATII RNA into sEVs, and the spread of SATII RNA through sEVs promotes the expression of inflammatory SASP genes. Additionally, high expression of YBX1 is associated with poor prognosis in breast and ovarian cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Tomonori Kamiya, Naoko Ohtani
Summary: More than 500 species of microbiota in the human intestine coexist with host cells in the liver, including immune cells. This review discusses the impact of gut microbial components and metabolites on liver cells, especially immune cells, and the mechanisms underlying gut microbiota-mediated liver carcinogenesis, as well as cancer prevention.
INTERNATIONAL IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Yoshimi Yukawa-Muto, Tomonori Kamiya, Hideki Fujii, Hiroshi Mori, Atsushi Toyoda, Ikuya Sato, Yusuke Konishi, Akiyoshi Hirayama, Eiji Hara, Shinji Fukuda, Norifumi Kawada, Naoko Ohtani
Summary: This study identified specific gut bacterial species abundant in patients with HE and verified their functions linked to HE pathophysiology. Targeting these bacteria could be a potentially effective strategy to treat HE.
HEPATOLOGY COMMUNICATIONS
(2022)
Review
Immunology
Naoko Ohtani
Summary: Cellular senescence is an irreversible cell cycle arrest state that suppresses tumorigenesis, but recent studies have revealed that senescent cells also secrete substances that alter the tissue environment and contribute to chronic inflammation and cancer. This secretion phenomenon, known as senescence-associated secretory phenotype (SASP), can be observed in vitro and in vivo. The production of SASP factors is mainly mediated through the cGAS-STING pathway, and there are also external triggers for SASP induction.
INFLAMMATION AND REGENERATION
(2022)
Article
Dermatology
Matthew J. Davis, Gokul Srinivasan, Rachael Chacko, Sophie Chen, Anish Suvarna, Louis J. Vaickus, Veronica C. Torres, Sassan Hodge, Eunice Y. Chen, Sarah Preum, Kimberley S. Samkoe, Brock C. Christensen, Matthew R. Leboeuf, Joshua J. Levy
Summary: The development and application of AI algorithms are of great significance for the removal of cSCC, as they can improve operational efficiency and accuracy, especially for moderately and poorly differentiated tumors/ neoplasms. Further improvement is needed to maintain sensitivity to surrounding tissue and determine anatomical positioning.
EXPERIMENTAL DERMATOLOGY
(2024)
Article
Dermatology
Lingjing Chen, Qing Yu, Feiying Guo, Xuewen Wang, Zhenying Cai, Qiang Zhou
Summary: This study investigated the role and mechanisms of NTS in stress-induced hair growth inhibition. The results demonstrated that NTS effectively counteracted hair growth inhibition caused by stress and regulated the expression of multiple genes related to hair growth at the transcriptional level.
EXPERIMENTAL DERMATOLOGY
(2024)
