Cellular Senescence & Lung Disease

Prof. Dr. Serge Adnot

Serge Adnot, MD PhD, is Professor of Physiology (School of Medicine, University Paris-Est-Creteil, France), where he heads the research group “Role of cellular senescence in respiratory diseases” at the INSERM Mondor Biomedical Research Institute. He is MD in the clinical functional tests department of the CHU Henri Mondor, which he led until 2018. He was jointly appointed in 2021 as a professor at the Institute for Lung Health (ILH) of Justus Liebig University (JLU) in Giessen, Germany, where he leads the research group “Cellular senescence and Lung Disease.”

He is focusing his research on the role for cell senescence in the pathogenesis of lung disease and/or as a new treatment target. Cell senescence consists in a stable proliferation arrest and the acquisition of a specific senescence-associated secretory phenotype (SASP) characterized by the release of inflammatory cytokines, immune modulators, proteases, pro-fibrotic factors and various effectors that can alter tissue organization and function. It is triggered by a myriad of stress constellations, which promote a DNA damage response leading to p53-dependent upregulation of the CDK inhibitor p21 and/or expression of p16, used as a reliable marker of senescent cells. Cell senescence is pivotal in various age-associated lung diseases.

The Adnot lab has pioneered the concept that chronic obstructive pulmonary disease (COPD) is associated with accelerated aging and that lung cell senescence is a major propeller of lung alterations. Recent major achievements include the identification of new therapeutic strategies for pulmonary hypertension, undescribed mechanism underlying the lung alterations of chronic obstructive lung disease, and work on cell senescence as a treatment target in several acute and chronic lung diseases. He has co-authored 247 publications and his h-index is 62 (11691 citations).

Scientific Program of the Professorship

Employing these tools and cooperation with several ILH scientists, the following major objectives will be addressed in the forthcoming 5-year period:Cell senescence occurs in a variety of physiological and pathological conditions including tissue remodeling, injury, cancer, and aging, where it can cause either detrimental or beneficial effects. Causality can be demonstrated by suppressing the SASP, blocking the establishment of the cell-senescence program through inactivation of p16 (a key component of the program) or, more conclusively, by selectively eliminating senescent cells and assessing the impact on the lung alterations. Senescent cells can be eliminated by engineering transgenic mouse models or by administering validated senolytic agents.

To this end, several senescence reporter-ablator mouse models have been developed by the S Adnot lab including mice expressing a killer gene construct driven by the p16 promoter (p16-ATTAC mice), mice with a floxed stop codon upstream to the ATTAC transgene with mCherry gene insertion near the ATTAC transgene, mice expressing telomerase or telomerase with an inactive catalytic site under the control of the p21 promoter (p21-mTert and p21-mTertci mice).

Employing these tools and cooperation with several ILH scientists, the following major objectives will be addressed in the forthcoming 5-year period:

A: Test whether Influenza A virus (IAV) or SARS-Cov2-induced lung-cell senescence is a major mechanism involved in the severity and duration of lung viral infection, and whether senescent lung cell persistence after infection underlies the development of post-viral lung disease.

  • Understand the temporal and topographic relations between senescent-cell accumulation and lung injury in Influenza A virus (IAV) and SARS-CoV-2 lung infection.
  • Explore the causal relationship between IAV- and SARS-CoV-2-induced lung-cell senescence on the development of lung pathology
  • Validate the concept of IAV-induced lung-cell senescence in human pathology


B: Decipher the role for lung cell senescence in lung emphysema

  • Map senescent-cell types in the lung from senescence reporter-ablator mouse models subjected to various stresses and in human lungs from patients with lung emphysema or COPD
  • Assess the potential impact of specific senescent lung cells on the pathogenesis of lung emphysema and on post-emphysema alveolar regeneration

C: Determine mechanisms involved in the cell senescence process that can be targeted pharmacologically.



Prof. Dr. Serge Adnot
Institute for Lung Health (ILH)
Justus Liebig University Giessen
Aulweg 130
35392 Giessen

Faculté de Santé
8, rue du Général Sarrail
94010, Creteil, France

Hopital Henri Mondor
Service de Physiologie Explorations Fonctionnelles
94010, Creteil, France

Tel: +33 (1) 49813701
Tel: +33 (1) 611290227



Ten most important publications

  1. Beaulieu D, Attwe A, Breau M, Lipskaia L, Marcos E, Born E, Huang J, Abid S, Derumeaux G, Houssaini A, Maitre B, Lefevre M, Vienney N, Bertolino P, Jaber S, Noureddine H, Goehrig D, Vindrieux D, Bernard D and Adnot S. Phospholipase A2 receptor 1 promotes lung cell senescence and emphysema in obstructive lung disease. Eur Respir J. 2021;58.
  2. Breau M, Houssaini A, Lipskaia L, Abid S, Born E, Marcos E, Czibik G, Attwe A, Beaulieu D, Palazzo A, Flaman JM, Bourachot B, Collin G, Tran Van Nhieu J, Bernard D, Mechta-Grigoriou F and Adnot S. The antioxidant N-acetylcysteine protects from lung emphysema but induces lung adenocarcinoma in mice. JCI Insight. 2019;4.
  3. Abid S, Marcos E, Parpaleix A, Amsellem V, Breau M, Houssaini A, Vienney N, Lefevre M, Derumeaux G, Evans S, Hubeau C, Delcroix M, Quarck R, Adnot S and Lipskaia L. CCR2/CCR5-mediated macrophage-smooth muscle cell crosstalk in pulmonary hypertension. Eur Respir J. 2019;54.
  4. Houssaini A, Breau M, Kebe K, Abid S, Marcos E, Lipskaia L, Rideau D, Parpaleix A, Huang J, Amsellem V, Vienney N, Validire P, Maitre B, Attwe A, Lukas C, Vindrieux D, Boczkowski J, Derumeaux G, Pende M, Bernard D, Meiners S and Adnot S. mTOR pathway activation drives lung cell senescence and emphysema. JCI Insight. 2018;3.
  5. Parpaleix A, Boyer L, Wiedemann A, Lacabaratz C, Margarit L, Enouf V, Le Corvoisier P, Lino A, Covali-Noroc A, Housset B, Chouaid C, Maitre B, Levy Y, Lelievre JD and Adnot S. Impaired humoral and cellular immune responses to influenza vaccination in chronic obstructive pulmonary disease patients. J Allergy Clin Immunol. 2017;140:1754-1757 e6.
  6. Mouraret N, Houssaini A, Abid S, Quarck R, Marcos E, Parpaleix A, Gary-Bobo G, Dubois-Rande JL, Derumeaux G, Boczkowski J, Delcroix M, Blasco MA, Lipskaia L, Amsellem V and Adnot S. Role for telomerase in pulmonary hypertension. Circulation. 2015;131:742-755.
  7. Amsellem V, Lipskaia L, Abid S, Poupel L, Houssaini A, Quarck R, Marcos E, Mouraret N, Parpaleix A, Bobe R, Gary-Bobo G, Saker M, Dubois-Rande JL, Gladwin MT, Norris KA, Delcroix M, Combadiere C and Adnot S. CCR5 as a treatment target in pulmonary arterial hypertension. Circulation. 2014;130:880-891.
  8. Mouraret N, Marcos E, Abid S, Gary-Bobo G, Saker M, Houssaini A, Dubois-Rande JL, Boyer L, Boczkowski J, Derumeaux G, Amsellem V and Adnot S. Activation of lung p53 by Nutlin-3a prevents and reverses experimental pulmonary hypertension. Circulation. 2013;127:1664-76.
  9. Dagouassat M, Gagliolo JM, Chrusciel S, Bourin MC, Duprez C, Caramelle P, Boyer L, Hue S, Stern JB, Validire P, Longrois D, Norel X, Dubois-Rande JL, Le Gouvello S, Adnot S and Boczkowski J. The cyclooxygenase-2-prostaglandin E2 pathway maintains senescence of chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med. 2013;187:703-14.
  10. Amsellem V, Gary-Bobo G, Marcos E, Maitre B, Chaar V, Validire P, Stern JB, Noureddine H, Sapin E, Rideau D, Hue S, Le Corvoisier P, Le Gouvello S, Dubois-Rande JL, Boczkowski J, Adnot S. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;184(12):1358-1366

Here you can find all ILH-publications