Review
Oncology
Daniel Otero-Albiol, Amancio Carnero
Summary: Cellular senescence is a complex physiological state characterized by proliferative arrest, with various functions beyond tumor suppression. Low oxygen conditions have been observed to increase the lifespan of mammalian cells and promote self-renewal and pluripotency in stem cells. Hypoxia facilitates senescence bypass, malignant transformation, and acquisition of stemness properties, contributing to tumor development and aggressiveness in cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Endocrinology & Metabolism
Christopher D. Wiley, Judith Campisi
Summary: Cellular senescence involves a permanent proliferative arrest and the release of biologically active molecules known as SASP. Studies show that senescence and SASP are sensitive to metabolic states, potentially driving phenotypes associated with metabolic dysfunction. Effective interventions may disrupt the feedback loop in which cellular senescence promotes metabolic diseases.
Article
Cell Biology
Alam Khan, Talukdar Mohammad Fahad, Tanjima Akther, Tanjeena Zaman, Md Faruk Hasan, Md Rafiqual Islam Khan, Mohammad Saiful Islam, Shuji Kishi
Summary: Carbofuran exposure synergistically accelerates cellular senescence and affects biological ageing in spns1 defective animals, as shown by accelerated yolk opaqueness, premature ageing phenotype, and shortened life span.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Katarzyna Malgorzata Kwiatkowska, Eleni Mavrogonatou, Adamantia Papadopoulou, Claudia Sala, Luciano Calzari, Davide Gentilini, Maria Giulia Bacalini, Daniele Dall'Olio, Gastone Castellani, Francesco Ravaioli, Claudio Franceschi, Paolo Garagnani, Chiara Pirazzini, Dimitris Kletsas
Summary: The aim of this study was to characterize DNA methylation patterns in replicative and induced senescence in different human cell types. Three epigenetic signatures were identified: cell type- and treatment-specific signature, cell type-specific senescence-related signature, and cell type-transversal replicative senescence-related signature. Cluster analysis revealed distinct DNA methylation patterns in replicative senescent cells, and enrichment in pathways related to the nervous system was shown. Despite no statistically significant evidence of age acceleration, a trend of increased biological age in replicative senescent cultures of all three cell types was observed. This work highlights the heterogeneity of senescent cells and their impact on tissue homeostasis.
Article
Biochemistry & Molecular Biology
Ji-Hwan Park, Sung Jin Ryu, Byung Ju Kim, Hyun-Ji Cho, Chi Hyun Park, Hyo Jei Claudia Choi, Eun-Jin Jang, Eun Jae Yang, Jeong-A Hwang, Seung-Hwa Woo, Jun Hyung Lee, Ji Hwan Park, Kyung-Mi Choi, Young-Yon Kwon, Cheol-Koo Lee, Joon Tae Park, Sung Chun Cho, Yun-Il Lee, Sung Bae Lee, Jeong A. Han, Kyung A. Cho, Min-Sik Kim, Daehee Hwang, Young-Sam Lee, Sang Chul Park
Summary: Impairment of nuclear-cytoplasmic trafficking (NCT) has been linked to cellular senescence, where signals transmission between the nucleus and cytoplasm is reduced as cells age. This disrupted communication may play a critical role in the aging process by affecting cell growth and division. Additional studies are needed to fully understand the mechanisms behind this phenomenon and its impact on cellular senescence.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Surgery
Elizabeth L. Thompson, Louise E. Pitcher, Laura J. Niedernhofer, Paul D. Robbins
Summary: Skin aging is caused by both extrinsic and intrinsic factors that lead to cellular senescence, resulting in pathological changes in the skin. The use of senolytics and senomorphics holds potential for improving skin aging and overall aging.
PLASTIC AND RECONSTRUCTIVE SURGERY
(2022)
Article
Cell Biology
Li-Bin Gao, Ya-Hong Wang, Zhi-Hua Liu, Yu Sun, Peng Cai, Qing Jing
Summary: The study demonstrated that the small molecule SR9009 effectively suppresses the senescence-associated secretory phenotype (SASP) by activating the NRF2 pathway, preventing cellular senescence. It also showed efficacy in inhibiting cellular aging and inflammation in mouse models.
Editorial Material
Biology
Na Yang, Payel Sen
Summary: Many senescence-associated features gradually emerge before cells cease to divide.
Article
Biology
Dorian V. Ziegler, Nadine Martin, David Bernard
Summary: The study explores the impact of mitochondria-endoplasmic reticulum contacts (MERCs) biology on cellular senescence and its relation to age-related diseases. It discusses the modulation of aging by MERCs and their role in regulating cellular senescence, potentially contributing to the aging process.
COMMUNICATIONS BIOLOGY
(2021)
Review
Endocrinology & Metabolism
Ulf Smith, Qian Li, Mikael Ryden, Kirsty L. Spalding
Summary: Cell senescence results in irreversible cell cycle arrest and the induction of a senescence-associated secretory phenotype (SASP), impacting cell proliferation and influencing the development of chronic diseases like diabetes and cardiovascular disease. Efforts to target senescent cells using senolytic compounds show promise in improving chronic disorders in experimental animal models.
INTERNATIONAL JOURNAL OF OBESITY
(2021)
Article
Multidisciplinary Sciences
Jamie L. Endicott, Paula A. Nolte, Hui Shen, Peter W. Laird
Summary: Researchers have provided experimental evidence showing that DNA methylation loss is directly driven by cell division, occurring in aging tissues and worsening in cancer. Blocking DNA replication can halt methylation loss. Ambient oxygen culture conditions increase the rate of methylation loss.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Haochun Guo, Jiajia Chen, Hanxu Yu, Lei Dong, Ran Yu, Qingju Li, Jian Song, Haoyu Chen, Haijun Zhang, Juan Pu, Wanpeng Wang
Summary: This study demonstrates the protective effect of 654-2 on radiation-induced lung injury (RILI). It mitigates pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis, while restoring epithelial cell proliferation ability and enhancing antioxidant capacity. The mechanism involves the activation of the Nrf2/ARE pathway and upregulation of antioxidant gene expression.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Vasco Lucas, Claudia Cavadas, Celia Alexandra Aveleira
Summary: The increase in life expectancy in developed countries has resulted in a rise in chronic aging-related diseases. Cellular senescence has been found to play a significant role in these pathologies, but its heterogeneous phenotype has hindered the discovery of reliable biomarkers. Strategies to prevent the harmful effects of senescent cell accumulation have shown potential, but their applicability to humans and senescence's role in physiological functions remain unclear.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Liguo Huang, Lit-Chein Chin, Koichi Kimura, Yasukazu Nakahata
Summary: This study found that human placental extract (HPE) has the ability to delay cellular senescence under oxidative stress conditions. By enhancing the expression of antioxidant genes and increasing the protein level of NRF2, a key molecule in the antioxidant pathway, HPE can mitigate oxidative stress-induced cellular damage.
Review
Genetics & Heredity
Kristopher Holloway, Kashfia Neherin, Kha Uyen Dam, Hong Zhang
Summary: Advancing age is a major risk factor for Alzheimer's disease. Cellular senescence, as a hallmark of aging, plays a significant role in the pathogenesis of Alzheimer's disease. This review provides an overview of the impact of cellular senescence on Alzheimer's disease pathogenesis, as well as its potential role in other neurodegenerative diseases.
Article
Geriatrics & Gerontology
Sara Lopez-Bellon, Sandra Rodriguez-Lopez, Jose A. Gonzalez-Reyes, M. Isabel Buron, Rafael de Cabo, Jose M. Villalba
Summary: The study showed that overexpression of CYB5R3 can activate mitochondrial function in skeletal muscle, delaying aging process and improving mitochondrial structure and autophagic recycling in old mice.
Article
Cell & Tissue Engineering
Xiaotong Hong, Joan Isern, Silvia Campanario, Eusebio Perdiguero, Ignacio Ramirez-Pardo, Jessica Segales, Pablo Hernansanz-Agustin, Andrea Curtabbi, Oleg Deryagin, Angela Pollan, Jose A. Gonzalez-Reyes, Jose M. Villalba, Marco Sandri, Antonio L. Serrano, Jose A. Enriquez, Pura Munoz-Canoves
Summary: Mitochondrial dynamics play a crucial role in the regenerative capacity of satellite cells. Aging or genetic impairment disrupts mitochondrial fission in satellite cells, leading to metabolic dysfunction and increased oxidative stress, resulting in muscle regenerative failure. Restoring mitochondrial dynamics can rescue impaired satellite cell function. These findings have implications for regeneration therapies in muscle aging.
Correction
Cell & Tissue Engineering
Hong Xiaotong, Joan Isern, Silvia Campanario, Eusebio Perdiguero, Ignacio Ramirez-Pardo, Jessica Segales, Pablo Hernansanz-Agustin, Andrea Curtabbi, Oleg Deryagin, Angela Pollan, Jose A. Gonzalez-Reyes, Jose M. Villalba, Marco Sandri, Antonio L. Serrano, Jose A. Enriquez, Pura Munoz-Canoves
Article
Oncology
Javier Frontinan-Rubio, Emilio Llanos-Gonzalez, Sonia Garcia-Carpintero, Juan Ramon Peinado, Inmaculada Ballesteros-Yanez, Margarita Villar Rayo, Jose de la Fuente, Victor M. Perez-Garcia, Luis A. Perez-Romasanta, Marcos Malumbres, Francisco J. Alcain, Mario Duran-Prado
Summary: This study proposes a therapeutic strategy for glioblastoma multiforme (GBM) using coenzyme Q(10) (CoQ(10)) as a pleiotropic factor that targets multiple hallmarks of the disease. The results show that CoQ(10) treatment decreases tumor volume, hypoxia, vascularization, and inflammatory cell infiltration while also inhibiting tumor cell migration and invasion by modulating the actin cytoskeleton and downregulating matrix metalloproteases (MMPs).
Article
Environmental Sciences
Silvana Arias, John R. Agudelo, Francisco J. Molina, Emilio Llanos-Gonzalez, Francisco J. Alcain, Rosario Ballesteros, Magin Lapuerta
Summary: This study investigates the unregulated emissions in gas and particles from a Euro 6b diesel engine, operated with four unconventional and advanced biofuels, blended with diesel fuel and pure hydro -treated vegetable oil. The results show that carbonyl emissions were higher than gaseous PAH emissions at low-speed phase, and both gas and particle emissions contribute to the toxicity associated with carcinogenic PAH.
Article
Geriatrics & Gerontology
Sara E. Espinoza, Sundeep Khosla, Joseph A. Baur, Rafael de Cabo, Nicolas Musi
Summary: The geroscience hypothesis suggests that targeting key hallmarks of aging can improve healthspan and prevent age-related diseases. Several pharmacological interventions, including senolytics, NAD(+) boosters, and metformin, are being studied for their potential benefits. Preclinical studies show that senolytic drugs improve healthspan in rodents, while increasing NAD(+) through supplementation appears to extend healthspan in model organisms. Metformin, on the other hand, has pleiotropic effects and is being examined for its potential to improve healthspan and prevent frailty in clinical trials. However, further research is needed to determine their efficacy, safety, target populations, and long-term outcomes.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Rheumatology
Carlos Perez-Sanchez, Alejandro Escudero-Contreras, Tomas Cerdo, Luz Marina Sanchez-Mendoza, Adrian Llamas-Urbano, Ivan Arias de la Rosa, Miguel Perez-Rodriguez, Laura Munoz-Barrera, Maria del Carmen Abalos-Aguilera, Nuria Barbarroja, Jerusalem Calvo, Rafaela Ortega-Castro, Desiree Ruiz-Vilchez, Juan Antonio Moreno, Maria Isabel Buron, Jose Antonio Gonzalez-Reyes, Eduardo Collantes-Estevez, Chary Lopez-Pedrera, Jose Manuel Villalba
Summary: Objective. This study analyzed NAD(+) metabolism in rheumatoid arthritis (RA) patients and its association with disease activity and clinical outcomes. The therapeutic potential of pharmacologic NAD(+) boosting was also evaluated. Reduced NAD(+) levels and altered activity of NAD(+)-related genes were found in RA patients. Anti-tumor necrosis factor (anti-TNF) therapy modulated NAD(+) levels and improved clinical response. NAD(+) boosters reduced oxidative stress, apoptosis, and inflammation in leukocytes from RA patients.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Emilio Llanos-Gonzalez, Francisco J. Sancho-Bielsa, Javier Frontinan-Rubio, Yoana Rabanal-Ruiz, Sonia Garcia-Carpintero, Eduardo Chicano, Isabel Ubeda-Banon, Alicia Flores-Cuadrado, Lydia Gimenez-Llort, Francisco Javier Alcain, Juan Ramon Peinado, Mario Duran-Prado
Summary: Despite the proteopathic nature of Alzheimer's disease, the spatiotemporal signature of disrupted protein modules in AD brains is poorly understood. By using MALDI-MSI and functional bioinformatic analysis, a protocol was developed to study how deregulated protein modules arise in an age-dependent manner in the AD mice model and identify which modules can be restored to a non-pathological condition through early intervention with ubiquinol.
Article
Cell Biology
Jayanta Kumar Das, Nirad Banskota, Julian Candia, Michael E. Griswold, Melissa Orenduff, Rafael de Cabo, David L. Corcoran, Sai Krupa Das, Supriyo De, Kim Marie Huffman, Virginia B. Kraus, William E. Kraus, Corby K. Martin, Susan B. Racette, Leanne M. Redman, Birgit Schilling, Daniel W. Belsky, Luigi Ferrucci
Summary: Using high-depth RNA-Seq analysis, this study found that caloric restriction (CR) positively affects skeletal muscle quality in humans and alters the gene expression and splicing profiles of biological pathways affected by CR in model organisms.
Article
Biochemistry & Molecular Biology
Luz Marina Sanchez-Mendoza, Carlos Perez-Sanchez, Sandra Rodriguez-Lopez, Chary Lopez-Pedrera, Miguel Calvo-Rubio, Rafael de Cabo, Maria I. Buron, Jose A. Gonzalez-Reyes, Jose M. Villalba
Summary: The study investigates the effect of sex on metabolic adaptations induced by overexpression of CYB5R3 and the modulation of key markers related to mitochondrial function in skeletal muscle. It was found that CYB5R3 overexpression leads to enhanced mitochondrial biogenesis and function, as well as increased mitochondrial abundance in skeletal muscle. These beneficial actions are predominantly observed in females, with differences in NADH levels and the abundance of cytochrome c and DRP-1. The results also show ultrastructural changes in transgenic females, including an increase in the number and size of mitochondria.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Hitoshi Watanabe, Wen Du, Jinsook Son, Lina Sui, Shun-ichiro Asahara, Irwin J. Kurland, Taiyi Kuo, Takumi Kitamoto, Yasutaka Miyachi, Rafael de Cabo, Domenico Accili
Summary: Sulfonylureas are effective and affordable antidiabetic drugs, but chronic use leads to secondary failure. Cytochrome b5 reductase 3 (Cyb5r3) down-regulation is identified as a mechanism of secondary SU failure and can be successfully reversed. Cyb5r3 activators can rescue secondary SU failure and potentially rehabilitate SU use in diabetes.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Geriatrics & Gerontology
Michel Bernier, Ignacio Navas Enamorado, Mari Carmen Gomez-Cabrera, Miguel Calvo-Rubio, Jose Antonio Gonzalez-Reyes, Nathan L. Price, Ana Belen Cortes-Rodriguez, Juan Carlos Rodriguez-Aguilera, Sandra Rodriguez-Lopez, Sarah J. Mitchell, Kelsey N. Murt, Krystle Kalafut, Katrina M. Williams, Christopher W. Ward, Joseph P. Stains, Gloria Brea-Calvo, Jose M. Villalba, Sonia Cortassa, Miguel A. Aon, Rafael de Cabo
Summary: This study investigates the effects of different exercise training modalities on skeletal muscle adaptation in adult and old mice. The results show that moderate intensity continuous training leads to improvements in body composition, blood glucose, and muscle strength in old mice, while the effects of high-intensity intermittent training are less clear. The study also reveals structural and functional adaptations in skeletal muscle in response to exercise training, as well as age-dependent metabolic remodeling. These findings highlight the importance of tailored exercise prescription for improving health and mitigating age-related muscle strength and function loss in the elderly.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase can utilize both Delta psi(m)-driven H+- and K+-transport to synthesize ATP under physiological conditions. The presence of K+ increases ATP synthesis rate in isolated mitochondria while also increasing oxygen consumption rate. The data obtained from purified F1Fo single molecule experiments are consistent with the functional data observed in intact mitochondria.
Article
Cell Biology
Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B. Zorov, H. Bradley Nuss, Yael Yaniv, Kenneth W. Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B. Gabelli, Miguel A. Aon, Sonia Cortassa, Steven J. Sollott
Summary: ATP synthase serves as the primary way for K+ to enter mitochondria, and its activity can be upregulated by endogenous survival-related proteins via IF1. The interaction between IF1 and Bcl-xL or Mcl-1 enhances ATP synthase's efficiency and limits ischemia-reperfusion injury.
