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108 results on '"Adnot, A."'

1. mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema

Author

Lipskaia, Larissa, Breau, Marielle, Cayrou, Christelle, Churikov, Dmitri, Braud, Laura, Jacquet, Juliette, Born, Emmanuelle, Fouillade, Charles, Curras-Alonso, Sandra, Bauwens, Serge, Jourquin, Frederic, Fiore, Frederic, Castellano, Rémy, Josselin, Emmanuelle, Sánchez-Ferrer, Carlota, Giovinazzo, Giovanna, Lachaud, Christophe, Gilson, Eric, Flores, Ignacio, Londono-Vallejo, Arturo, Adnot, Serge, and Géli, Vincent

Published
2024
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2. A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression

Author

Joanna Czarnecka-Herok, Kexin Zhu, Jean-Michel Flaman, Delphine Goehrig, Mathieu Vernier, Gabriela Makulyte, Aline Lamboux, Helena Dragic, Muriel Rhinn, Jean-Jacques Médard, Gilles Faury, Philippe Bertolino, Vincent Balter, Romain Debret, Serge Adnot, Nadine Martin, and David Bernard

Subjects
Cellular senescence, ELN, HMOX1, ROS, Iron, PHF8, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging, fostering the onset and progression of age-related diseases and overall aging, and has so far never been linked with elastin. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts or by knockout in mouse embryonic fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. Moreover, the induction of HMOX1 depends on p53 and NRF2 transcription factors, and leads to an increase in iron, further mediating ELN downregulation-induced senescence. Screening of iron-dependent DNA and histones demethylases revealed a role for histone PHF8 demethylase in mediating ELN downregulation-induced senescence. Collectively, these results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism involving a ROS/HMOX1/iron accumulation/PHF8 histone demethylase pathway reprogramming gene expression towards a senescence program.

Published
2024
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3. Combined effects of smoking and HIV infection on the occurrence of aging-related manifestations

Author

Laurent Boyer, Sonia Zebachi, Sébastien Gallien, Laurent Margarit, Bruno Ribeiro Baptista, José-Luis Lopez-Zaragoza, Thomas D’Humières, Françoise Zerah, Sophie Hue, Geneviève Derumeaux, Serge Adnot, Etienne Audureau, and Jean-Daniel Lelièvre

Subjects
Medicine, Science
Abstract

Abstract Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with

Published
2023
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4. Recent historic increase of infant mortality in France: A time-series analysis, 2001 to 2019

Author

Trinh, Nhung TH, de Visme, Sophie, Cohen, Jérémie F, Bruckner, Tim, Lelong, Nathalie, Adnot, Pauline, Rozé, Jean-Christophe, Blondel, Béatrice, Goffinet, François, Rey, Grégoire, Ancel, Pierre-Yves, Zeitlin, Jennifer, and Chalumeau, Martin

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Pediatric, Good Health and Well Being, Infant mortality, Joinpoints regression, Interrupted time-series analysis
Abstract

BackgroundThe infant mortality rate (IMR) serves as a key indicator of population health.MethodsWe used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2001 to 2019 to calculate IMR aggregated by month. We ran joinpoint regressions to identify inflection points and assess the linear trend of each segment. Exploratory analyses were performed for overall IMR, as well as by age at death subgroups (early neonatal [D0-D6], late neonatal [D7-27], and post-neonatal [D28-364]), and by sex. We performed sensitivity analyses by excluding deaths at D0 and using other time-series modeling strategies.ResultsOver the 19-year study period, 53,077 infant deaths occurred, for an average IMR of 3·63/1000 (4·00 in male, 3·25 in female); 24·4% of these deaths occurred during the first day of life and 47·8% during the early neonatal period. Joinpoint analysis identified two inflection points in 2005 and 2012. The IMR decreased sharply from 2001 to 2005 (slope: -0·0167 deaths/1000 live births/month; 95%CI: -0·0219 to -0·0116) and then decreased slowly between 2005 and 2012 (slope: -0·0041; 95%CI: -0·0065 to -0·0016). From 2012 onwards, a significant increase in IMR was observed (slope: 0·0033; 95%CI: 0·0011 to 0·0056). Subgroup analyses indicated that these trends were driven notably by an increase in the early neonatal period. Sensitivity analyses provided consistent results.InterpretationThe recent historic increase in IMR since 2012 in France should prompt urgent in-depth investigation to understand the causes and prepare corrective actions.FundingNo financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Published
2022

7. Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters

Author

Delval, Lou, Hantute-Ghesquier, Aline, Sencio, Valentin, Flaman, Jean Michel, Robil, Cyril, Angulo, Fabiola Silva, Lipskaia, Larissa, Çobanoğlu, Ozmen, Lacoste, Anne-Sophie, Machelart, Arnaud, Danneels, Adeline, Corbin, Mathieu, Deruyter, Lucie, Heumel, Séverine, Idziorek, Thierry, Séron, Karin, Sauve, Florent, Bongiovanni, Antonino, Prévot, Vincent, Wolowczuk, Isabelle, Belouzard, Sandrine, Saliou, Jean-Michel, Gosset, Philippe, Bernard, David, Rouillé, Yves, Adnot, Serge, Duterque-Coquillaud, Martine, and Trottein, François

Published
2023
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10. Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction

Author

Daigo Sawaki, Yanyan Zhang, Amel Mohamadi, Maria Pini, Zaineb Mezdari, Larissa Lipskaia, Suzain Naushad, Lucille Lamendour, Dogus Murat Altintas, Marielle Breau, Hao Liang, Maissa Halfaoui, Thaïs Delmont, Mathieu Surenaud, Déborah Rousseau, Takehiko Yoshimitsu, Fawzia Louache, Serge Adnot, Corneliu Henegar, Philippe Gual, Gabor Czibik, and Geneviève Derumeaux

Subjects
Aging, Immunology, Medicine
Abstract

Adipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction. Here, we show that ATMs (a) acquire a senescence-like phenotype during chronological aging; (b) display a global decline of basic macrophage functions such as efferocytosis, an essential process to preserve AT homeostasis by clearing dysfunctional or apoptotic cells; and (c) promote AT remodeling and dysfunction. Importantly, we uncover a major role for the age-associated accumulation of osteopontin (OPN) in these processes in visceral AT. Consistently, loss or pharmacologic inhibition of OPN and bone marrow transplantation of OPN–/– mice attenuate the ATM senescence-like phenotype, preserve efferocytosis, and finally restore healthy AT homeostasis in the context of aging. Collectively, our findings implicate pharmacologic OPN inhibition as a viable treatment modality to counter ATM senescence-mediated AT remodeling and dysfunction during aging.

Published
2023
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15. Piezo1 in pulmonary arterial smooth muscle cells – A critical player for the development of pulmonary hypertension

Author

Abid, S., primary, Houssaini, A., additional, Knoepp, F., additional, Born, E., additional, Marcos, E., additional, Lipskaia, L., additional, Arhatte, M., additional, Glogowska, E., additional, Vienney, N., additional, Kraut, S., additional, Quanz, K., additional, Fenner-Nau, D., additional, Weissmann, N., additional, Honoré, E., additional, and Adnot, S., additional

Published
2024
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16. Cell senescence in pulmonary hypertension

Author

Born, Emmanuelle, primary, Lipskaia, Larissa, additional, Abid, Shariq, additional, Houssaini, Amal, additional, Breau, Marielle, additional, Beaulieu, Delphine, additional, Marcos, Elisabeth, additional, and Adnot, Serge, additional

Published
2022
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17. Contributors

Author

Abid, Shariq, primary, Adnot, Serge, additional, Agusti, Alvar, additional, Beaulieu, Delphine, additional, Bhushan, Anil, additional, Bird, Thomas G., additional, Born, Emmanuelle, additional, Breau, Marielle, additional, Chin, Alexander F., additional, Elisseeff, Jennifer H., additional, Erlangga, Zulrahman, additional, Evangelou, Konstantinos, additional, Faner, Rosa, additional, Farr, Joshua N., additional, Georgakopoulou, Eleni, additional, González-Gualda, Estela, additional, Gorgoulis, Vassilis G., additional, Gray-Gaillard, Elise, additional, Han, Jin, additional, Hernandez-Gonzalez, Fernanda, additional, Houssaini, Amal, additional, Jensen, Michael D., additional, Jurk, Diana, additional, Katsuumi, Goro, additional, Khosla, Sundeep, additional, Kiourtis, Christos, additional, Kirkland, James L., additional, Kovatcheva, Marta, additional, Lipskaia, Larissa, additional, López-Domínguez, Jose Alberto, additional, Macías, David, additional, Marcos, Elisabeth, additional, Maus, Mate, additional, Melk, Anette, additional, Meyer, Kathleen, additional, Michel, John, additional, Minamino, Tohru, additional, Miwa, Satomi, additional, Monroe, David G., additional, Muñoz-Espín, Daniel, additional, Ou, Hui-Ling, additional, Palmer, Allyson K., additional, Saito, Nayuta, additional, Schmitt, Roland, additional, Sellares, Jacobo, additional, Serrano, Manuel, additional, Sung, Myong-Hee, additional, Tchkonia, Tamara, additional, Thompson, Peter J., additional, von Zglinicki, Thomas, additional, Wan, Tengfei, additional, and Zhang, Peisu, additional

Published
2022
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18. Recent historic increase of infant mortality in France: A time-series analysis, 2001 to 2019

Author

Nhung T.H. Trinh, Sophie de Visme, Jérémie F. Cohen, Tim Bruckner, Nathalie Lelong, Pauline Adnot, Jean-Christophe Rozé, Béatrice Blondel, François Goffinet, Grégoire Rey, Pierre-Yves Ancel, Jennifer Zeitlin, and Martin Chalumeau

Subjects
Infant mortality, Joinpoints regression, Interrupted time-series analysis, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The infant mortality rate (IMR) serves as a key indicator of population health. Methods: We used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2001 to 2019 to calculate IMR aggregated by month. We ran joinpoint regressions to identify inflection points and assess the linear trend of each segment. Exploratory analyses were performed for overall IMR, as well as by age at death subgroups (early neonatal [D0-D6], late neonatal [D7-27], and post-neonatal [D28-364]), and by sex. We performed sensitivity analyses by excluding deaths at D0 and using other time-series modeling strategies. Results: Over the 19-year study period, 53,077 infant deaths occurred, for an average IMR of 3·63/1000 (4·00 in male, 3·25 in female); 24·4% of these deaths occurred during the first day of life and 47·8% during the early neonatal period. Joinpoint analysis identified two inflection points in 2005 and 2012. The IMR decreased sharply from 2001 to 2005 (slope: -0·0167 deaths/1000 live births/month; 95%CI: -0·0219 to -0·0116) and then decreased slowly between 2005 and 2012 (slope: -0·0041; 95%CI: -0·0065 to -0·0016). From 2012 onwards, a significant increase in IMR was observed (slope: 0·0033; 95%CI: 0·0011 to 0·0056). Subgroup analyses indicated that these trends were driven notably by an increase in the early neonatal period. Sensitivity analyses provided consistent results. Interpretation: The recent historic increase in IMR since 2012 in France should prompt urgent in-depth investigation to understand the causes and prepare corrective actions. Funding: No financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Published
2022
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20. Early Mortality in Infants Born with Neonatally Operated Congenital Heart Defects and Low or Very-Low Birthweight: A Systematic Review and Meta-Analysis

Author

Neil Derridj, Ali Ghanchi, Damien Bonnet, Pauline Adnot, Makan Rahshenas, Laurent J. Salomon, Jérémie F. Cohen, and Babak Khoshnood

Subjects
congenital heart defects, systematic review, meta-analysis, low birth weight, hypoplastic left heart syndrome, mortality, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Mortality outcomes of children with isolated neonatally operated congenital heart defects (CHDs) born with a low (LBW), moderately low (MLBW) or very-low birthweight (VLBW) remain ambiguous. We searched Medline and Embase (inception until October 2021) and included studies that evaluated early mortality. The risk of bias was assessed using the Critical Appraisal Skills Program cohort checklist. Meta-analysis involved random-effects models. We explored variability in mortality across birthweight subgroups, CHD types, and study designs. From 2035 reports, we included 23 studies in qualitative synthesis, and the meta-analysis included 11 studies (1658 CHD cases), divided into 30 subcohorts. The risk of bias was low in 4/11 studies included in the meta-analysis. Summary mortality before discharge or within one month after surgery was 37% (95%CI 27–47). Early mortality varied by birthweight (VLBW 56%, MLBW 15%, LBW 16%; p = 0.003) and CHD types (hypoplastic left heart syndrome (HLHS) 50%, total anomalous pulmonary venous return (TAPVR) 47%, transposition of the great arteries (TGA) 34%, coarctation of the aorta (CoA) 16%; p = 0.13). Mortality was higher in population-based studies (49% vs. 10%; p = 0.006). One-third of infants born with neonatally operated isolated CHDs and LBW, MLBW, or VLBW died within 30 days after surgery. Mortality varied across infant and study characteristics. These results may help clinicians assess neonatal prognosis. PROSPERO registration CRD42020170289.

Published
2023
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23. Loss of Pla2r1 decreases cellular senescence and age‐related alterations caused by aging and Western diets

Author

Massemin, Amélie, primary, Goehrig, Delphine, additional, Flaman, Jean‐Michel, additional, Jaber, Sara, additional, Griveau, Audrey, additional, Djebali, Sophia, additional, Marcos, Elisabeth, additional, Payen, Léa, additional, Marvel, Jacqueline, additional, Parent, Romain, additional, Adnot, Serge, additional, Bertolino, Philippe, additional, Rieusset, Jennifer, additional, Tortereau, Antonin, additional, Vindrieux, David, additional, and Bernard, David, additional

Published
2023
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25. Osteopontin promotes age-related adipose tissue remodeling through senescence-associated macrophage dysfunction

Author

Sawaki, Daigo, primary, Zhang, Yanyan, additional, Mohamadi, Amel, additional, Pini, Maria, additional, Mezdari, Zaineb, additional, Lipskaia, Larissa, additional, Naushad, Suzain, additional, Lamendour, Lucille, additional, Altintas, Dogus Murat, additional, Breau, Marielle, additional, Liang, Hao, additional, Halfaoui, Maissa, additional, Delmont, Thaïs, additional, Surenaud, Mathieu, additional, Rousseau, Déborah, additional, Yoshimitsu, Takehiko, additional, Louache, Fawzia, additional, Adnot, Serge, additional, Henegar, Corneliu, additional, Gual, Philippe, additional, Czibik, Gabor, additional, and Derumeaux, Geneviève, additional

Published
2023
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30. Evidence That SARS-CoV-2 Induces Lung Cell Senescence: Potential Impact on COVID-19 Lung Disease

Author

Emmanuelle Born, Jean-Michel Flaman, Charles Fouillade, Roger Le Grand, Larissa Lipskaia, Serge Adnot, Quentin Pascal, Arturo London-Vallejo, David Bernard, Pauline Maisonnasse, Valentin Sencio, François Trottein, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, ATMEL [Rousset], CHU Henri Mondor, Supported by grants from the ANR AAP Flash COVID19 under reference AM-CoV-Path (RLG), ANR AAP Recherche-Action COVID19 under reference SENOCOVID - ANR 20 COV3 0006, ANR (Lustra), ANR (Influenzaging), the Institut National Du Cancer (INCA), EDF (CT9818), the Fondation pour la Recherche Médicale (FRM), and La Ligue contre le Cancer-Paris (RS21/75-24)., ANR-20-COVI-0021,AM-Cov-Path,Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention(2020), ANR-20-COV3-0006,SENOCOVID,La sénescence cellulaire pulmonaire comme cible pour contrôler le COVID-19(2020), ANR-19-CE14-0015,Lustra,Fibrogenèse pulmonaire: approche systémique par transcriptomique spatiale(2019), ANR-20-CE14-0023,INFLUENZAGING,La sénescence cellulaire pulmonaire induite par le virus influenza: déterminant de la sévérité de l'atteinte respiratoire et de l'induction des maladies pulmonaires chroniques(2020), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Gestionnaire, HAL Sorbonne Université 5, Pathogénèse de l'infection SARS-Cov-2 dans un modèle de primates non humains : un modèle pour les traitements et la prévention - - AM-Cov-Path2020 - ANR-20-COVI-0021 - COVID-19 - VALID, La sénescence cellulaire pulmonaire comme cible pour contrôler le COVID-19 - - SENOCOVID2020 - ANR-20-COV3-0006 - COVID-19 - VALID, Fibrogenèse pulmonaire: approche systémique par transcriptomique spatiale - - Lustra2019 - ANR-19-CE14-0015 - AAPG2019 - VALID, La sénescence cellulaire pulmonaire induite par le virus influenza: déterminant de la sévérité de l'atteinte respiratoire et de l'induction des maladies pulmonaires chroniques - - INFLUENZAGING2020 - ANR-20-CE14-0023 - AAPG2020 - VALID, and CHU Henri Mondor [Créteil]

Subjects
Lung Diseases, Pulmonary and Respiratory Medicine, Senescence, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clinical Biochemistry, Cell, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Animals, Humans, Lung, Molecular Biology, Cellular Senescence, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Potential impact, SARS-CoV-2, COVID-19, Cell Biology, Virology, 3. Good health, Macaca fascicularis, medicine.anatomical_structure, 030228 respiratory system, Lung disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience

Published
2022

31. Eliminating senescent cells can promote pulmonary hypertension development and progression

Author

Emmanuelle Born, Larissa Lipskaia, Marielle Breau, Amal Houssaini, Delphine Beaulieu, Elisabeth Marcos, Remi Pierre, Marcio Do Cruzeiro, Marine Lefevre, Genevieve Derumeaux, Dmitry V. Bulavin, Marion Delcroix, Rozenn Quarck, Virinder Reen, Jesus Gil, David Bernard, Jean-Michel Flaman, Serge Adnot, and Shariq Abid

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models. Methods: We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models. We monitored p16 activation by luminescence imaging in p16-luciferase (p16 LUC/+ ) knock-in mice. SC clearance was obtained by a suicide gene (p16 promoter–driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell-permeable FOXO4-p53 interfering peptide [FOXO4-DRI]), and p16 inactivation in p16 LUC/LUC mice. We investigated pulmonary hypertension in mice exposed to normoxia, chronic hypoxia, or hypoxia+Sugen, mice overexpressing the serotonin transporter (SM22-5-HTT + ), and rats given monocrotaline. Results: Patients with pulmonary arterial hypertension compared with controls exhibited high lung p16, p21, and γ-H2AX protein levels, with abundant vascular cells costained for p16, γ-H2AX, and 53BP1. Hypoxia increased thoracic bioluminescence in p16 LUC/+ mice. In wild-type mice, hypoxia increased lung levels of senescence and DNA-damage markers, senescence-associated secretory phenotype components, and p16 staining of pulmonary endothelial cells (P-ECs, 30% of lung SCs in normoxia), and pulmonary artery smooth muscle cells. SC elimination by suicide gene or ABT263 increased the right ventricular systolic pressure and hypertrophy index, increased vessel remodeling (higher dividing proliferating cell nuclear antigen–stained vascular cell counts during both normoxia and hypoxia), and markedly decreased lung P-ECs. Pulmonary hemodynamic alterations and lung P-EC loss occurred in older p16 LUC/LUC mice, wild-type mice exposed to Sugen or hypoxia+Sugen, and SM22-5-HTT + mice given either ABT263 or FOXO4-DRI, compared with relevant controls. The severity of monocrotaline-induced pulmonary hypertension in rats was decreased slightly by ABT263 for 1 week but was aggravated at 3 weeks, with loss of P-ECs. Conclusions: Elimination of senescent P-ECs by senolytic interventions may worsen pulmonary hemodynamics. These results invite consideration of the potential impact on pulmonary vessels of strategies aimed at controlling cell senescence in various contexts.

Published
2022

33. Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lung

Author

Larissa Lipskaia, Marielle Breau, Christelle Cayrou, Dmitri Churikov, Laura Braud, Charles Fouillade, Sandra Curras-Alonso, Serge Bauwens, Frederic Jourquin, Frederic Fiore, Rémy Castellano, Emmanuelle Josselin, Carlota Sánchez-Ferrer, Giovanna Giovinazzo, Eric Gilson, Ignacio Flores, Arturo Londono-Vallejo, Serge Adnot, Vincent Géli, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Abstract

Telomerase is required for long-term cell proliferation and linked to stem cells. This is evident in the lung where short telomeres are associated with lung dysfunction. We constructed a mouse model in which the telomerase (Tert) is expressed from the p21Cdkn1apromoter. We found that this peculiar Tert expression curb age-related emphysema and pulmonary perivascular fibrosis in old mice. In old mice lungs, such Tert expression preferentially occurs in endothelial cells where it reduces the number of senescent endothelial cells. Remarkably, we report that Tert counteracts the age-related decline in capillary density. This was associated with an increased number of Cd34+ cells identified as a subclass of capillary cells with proliferative capacity. Expression of catalytically inactiveTertneither prevents the decline of capillary density in old mice nor protects against age-related emphysema and fibrosis. These findings reveal that telomerase decreases age-decline of pulmonary functions by sustaining microvasculature regeneration and outgrowth.

Published
2022

34. Induction of telomerase in p21-positive cells counteracts capillaries rarefaction in aging mice lung

Author

Lipskaia, Larissa, primary, Breau, Marielle, additional, Cayrou, Christelle, additional, Churikov, Dmitri, additional, Braud, Laura, additional, Fouillade, Charles, additional, Curras-Alonso, Sandra, additional, Bauwens, Serge, additional, Jourquin, Frederic, additional, Fiore, Frederic, additional, Castellano, Rémy, additional, Josselin, Emmanuelle, additional, Sánchez-Ferrer, Carlota, additional, Giovinazzo, Giovanna, additional, Gilson, Eric, additional, Flores, Ignacio, additional, Londono-Vallejo, Arturo, additional, Adnot, Serge, additional, and Géli, Vincent, additional

Published
2022
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38. In vitro rescue of the bile acid transport function of some ABCB11 variants by CFTR potentiators: a targeted pharmacotherapy in progressive familial intrahepatic cholestasis type 2

Author

Mareux, Elodie, primary, Lapalus, Martine, additional, Almes, Marion, additional, Adnot, Pauline, additional, Lakli, Mounia, additional, Saad, Amel Ben, additional, Decout, Jean-Luc, additional, Falguières, Thomas, additional, Callebaut, Isabelle, additional, Gonzalès, Emmanuel, additional, and Jacquemin, Emmanuel, additional

Published
2022
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40. Recent historic increase of infant mortality in France: A time-series analysis, 2001 to 2019

Author

Trinh, Nhung T.H., primary, de Visme, Sophie, additional, Cohen, Jérémie F., additional, Bruckner, Tim, additional, Lelong, Nathalie, additional, Adnot, Pauline, additional, Rozé, Jean-Christophe, additional, Blondel, Béatrice, additional, Goffinet, François, additional, Rey, Grégoire, additional, Ancel, Pierre-Yves, additional, Zeitlin, Jennifer, additional, and Chalumeau, Martin, additional

Published
2022
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42. Telomerase Prevents Emphysema in Old Mice by Sustaining Subpopulations of Endothelial and AT2 Cells

Author

Marielle Breau, Christelle Cayrou, Dmitri Churikov, Charles Fouillade, Sandra Curras-Alonso, Serge Bauwens, Frederic Jourquin, Laura Braud, Frederic Fiore, Rémy Castellano, Emmanuelle Josselin, Carlota Sánchez-Ferrer, Giovanna Giovinazzo, Eric Gilson, Ignacio Flores, Arturo Londono-Vallejo, Serge Adnot, Vincent Géli, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de neurosciences intégratives et cognitives (CNIC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), and CAYROU, CHRISTELLE

Subjects
0303 health sciences, telomere, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], senescence, aging, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], respiratory system, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], lung, stem cell, 03 medical and health sciences, 0302 clinical medicine, emphysema, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Telomerase, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Accumulation of senescent cells has been causally linked to the development of age-related pathologies. Here, we characterized a new mouse model (p21+/Tert) whose telomerase (TERT) is expressed from the p21 promoter that can be activated in response to telomere dysfunction. Lung parenchyma from p21+/Tert old mice accumulated fewer senescent cells with age and this correlated with a reduction in age-related alveolar space enlargement, a feature of pulmonary emphysema. This protection against emphysema depends on TERT catalytic activity and is associated with increased proliferation of pulmonary endothelial cells (EC) and capillary density. Single-cell RNA sequencing of lung cells revealed that TERT expression was associated with the enrichment of ECs expressing genes involved in vessel regeneration and in AT2 cells overexpressing S/G2M markers. These findings indicate that p21-promoter-dependent expression of catalytically active telomerase prevents emphysema by sustaining the proliferation of subclasses of EC and AT2 cells.

Published
2022

46. Contributors

Author

Shariq Abid, Serge Adnot, Alvar Agusti, Delphine Beaulieu, Anil Bhushan, Thomas G. Bird, Emmanuelle Born, Marielle Breau, Alexander F. Chin, Jennifer H. Elisseeff, Zulrahman Erlangga, Konstantinos Evangelou, Rosa Faner, Joshua N. Farr, Eleni Georgakopoulou, Estela González-Gualda, Vassilis G. Gorgoulis, Elise Gray-Gaillard, Jin Han, Fernanda Hernandez-Gonzalez, Amal Houssaini, Michael D. Jensen, Diana Jurk, Goro Katsuumi, Sundeep Khosla, Christos Kiourtis, James L. Kirkland, Marta Kovatcheva, Larissa Lipskaia, Jose Alberto López-Domínguez, David Macías, Elisabeth Marcos, Mate Maus, Anette Melk, Kathleen Meyer, John Michel, Tohru Minamino, Satomi Miwa, David G. Monroe, Daniel Muñoz-Espín, Hui-Ling Ou, Allyson K. Palmer, Nayuta Saito, Roland Schmitt, Jacobo Sellares, Manuel Serrano, Myong-Hee Sung, Tamara Tchkonia, Peter J. Thompson, Thomas von Zglinicki, Tengfei Wan, and Peisu Zhang

Published
2022

49. Telomere shortening during human septic shock: influence of sepsis mediators, role in organ failures, and septic myocardial dysfunction

Author

Serge Adnot, Armand Mekontso Dessap, Laurent Boyer, Keyvan Razazi, Elisabeth Marcos, and Sophie Hue

Subjects
medicine.medical_specialty, RC86-88.9, business.industry, Septic shock, Multiple Organ Failure, Medical emergencies. Critical care. Intensive care. First aid, Critical Care and Intensive Care Medicine, medicine.disease, Shock, Septic, Telomere, Sepsis, Internal medicine, Research Letter, Cardiology, Humans, Medicine, Cardiomyopathies, business, Telomere Shortening
Published
2021

50. Variations in Guidelines for Diagnosis of Child Physical Abuse in High-Income Countries

Author

Caroline Rey-Salmon, Slimane Allali, Per Ashorn, Thomas Fischbach, Elise Launay, Daniela Karall, Federica Zanetto, Jérémie F. Cohen, Christèle Gras-Le Guen, Yacine Refes, Nathalie Vabres, Martin Chalumeau, Paolo Ramelli, Helena Porfirio, Flora Blangis, Andreas Werner, Catherine Adamsbaum, Pauline Adnot, Patrick Theisen, Jacob Urkin, and Concepción Sanchez-Pina

Subjects
Male, Parents, medicine.medical_specialty, Skeletal survey, Pediatrics, Diagnosis, Differential, Hematoma, Return to Work, medicine, Medical imaging, Humans, Child Abuse, Intensive care medicine, Child, Original Investigation, medicine.diagnostic_test, business.industry, Clinical Laboratory Techniques, Developed Countries, Research, Infant, Magnetic resonance imaging, General Medicine, medicine.disease, Online Only, Systematic review, Bone scintigraphy, Physical Abuse, Radiological weapon, Abdominal ultrasonography, Child, Preschool, Practice Guidelines as Topic, Wounds and Injuries, Female, business
Abstract

Key Points Question Are clinical guidelines for the early detection and diagnostic workup of child physical abuse complete, clear, and consistent across high-income countries? Findings In this systematic review that included 20 clinical guidelines issued in 15 countries, guidelines were clear but incomplete and discrepant, particularly in the definition of sentinel injuries and in recommendations for exploratory laboratory testing and advanced imaging. Meaning This systematic review found a lack of standardized guidelines for the identification and management of child physical abuse, which may contribute to practice variation., This systematic review evaluates the completeness, clarity, and consistency of guidelines from high-income countries for the detection and diagnosis of child physical abuse., Importance The highly variable practices observed regarding the early detection and diagnostic workup of suspected child physical abuse contribute to suboptimal care and could be partially related to discrepancies in clinical guidelines. Objective To systematically evaluate the completeness, clarity, and consistency of guidelines for child physical abuse in high-income countries. Evidence Review For this systematic review, national or regional guidelines that were disseminated from 2010 to 2020 related to the early detection and diagnostic workup of child physical abuse in infants aged 2 years or younger by academic societies or health agencies in high-income countries were retrieved. The definitions of sentinel injuries and the recommended diagnostic workup (imaging and laboratory tests) for child physical abuse were compared. Data were analyzed from July 2020 to February 2021. Findings Within the 20 included guidelines issued in 15 countries, 168 of 408 expected statements (41%) were missing and 10 statements (4%) were unclear. Among 16 guidelines characterizing sentinel injuries, all of them included skin injuries, such as bruises, hematoma, or burns, but only 8 guidelines (50%) included intraoral injuries and fractures. All 20 guidelines agreed on the indication for radiological skeletal survey, head computed tomography, and head magnetic resonance imaging but differed for those of bone scintigraphy, follow-up skeletal survey, spinal magnetic resonance imaging, cranial ultrasonography, chest computed tomography, and abdominal ultrasonography and computed tomography. Additionally, 16 guidelines agreed on exploring primary hemostasis and coagulation but not on the tests to perform, and 8 guidelines (50%) mentioned the need to investigate bone metabolism. Conclusions and Relevance These findings suggest that guidelines for the diagnosis of child physical abuse in infants were often clear but lacked completeness and were discrepant on major issues. These results may help identify priorities for well-designed original diagnostic accuracy studies, systematic reviews, or an international consensus process to produce clear and standardized guidelines to optimize practices and infant outcomes.

Published
2021

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