2. Academic Validation
  3. Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice

  • Nat Aging. 2024 Sep;4(9):1231-1248. doi: 10.1038/s43587-024-00663-7.
Sara Zumerle # 1 2,  Miles Sarill # 1 3,  Miriam Saponaro 1 2 4,  Manuel Colucci 5 6 7,  Liliana Contu 1 2,  Edoardo Lazzarini 8 9,  Roberta Sartori 1 10,  Camilla Pezzini 1 10,  Anna Rinaldi 11 12,  Anna Scanu 13,  Jacopo Sgrignani 14,  Patrizia Locatelli 14,  Marianna Sabbadin 1 2 15,  Aurora Valdata 5 6 16,  Daniela Brina 5 6,  Isabella Giacomini 1 3,  Beatrice Rizzo 1 3 15,  Alessandra Pierantoni 1 3 17,  Saman Sharifi 1 2 3,  Silvia Bressan 1 3 5 6,  Claudia Altomare 8 9,  Yulia Goshovska 8 9,  Chiara Giraudo 2 18,  Roberto Luisetto 19,  Luca Iaccarino 2,  Cristina Torcasio 11 12,  Simone Mosole 5 6,  Emiliano Pasquini 5 6,  Andrea Rinaldi 5 6,  Laura Pellegrini 5 6,  Gregorio Peron 3 20,  Matteo Fassan 2 15,  Stefano Masiero 13,  Andrea Maria Giori 21,  Stefano Dall'Acqua 3,  Johan Auwerx 22,  Pietro Cippà 6 11 12,  Andrea Cavalli 6 14,  Marco Bolis 5 6,  Marco Sandri 1 10,  Lucio Barile 8 9,  Monica Montopoli 23 24,  Andrea Alimonti 25 26 27 28 29 30
Affiliations

Affiliations

  • 1 Veneto Institute of Molecular Medicine, Padova, Italy.
  • 2 Department of Medicine, University of Padova, Padova, Italy.
  • 3 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • 4 Department of Urology and Pediatric Urology, University Medical Center Bonn (UKB), Bonn, Germany.
  • 5 Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • 6 Università della Svizzera italiana, Lugano, Switzerland.
  • 7 Faculty of Biology and Medicine, University of Lausanne UNIL, Lausanne, Switzerland.
  • 8 Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • 9 Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland.
  • 10 Department of Biomedical Sciences, University of Padova, Padova, Italy.
  • 11 Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • 12 Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • 13 Department of Neuroscience, Rehabilitation Unit, University of Padova, Padova, Italy.
  • 14 Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • 15 Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
  • 16 Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland.
  • 17 Institute for Research on Cancer and Aging, Nice, France.
  • 18 Department of Cardiac, Thoracic, Vascular Sciences and Public Health - DCTV, University of Padova, Padova, Italy.
  • 19 Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
  • 20 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  • 21 R&D Department, IBSA Farmaceutici Italia, Lodi, Italy.
  • 22 Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • 23 Veneto Institute of Molecular Medicine, Padova, Italy. [email protected].
  • 24 Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy. [email protected].
  • 25 Veneto Institute of Molecular Medicine, Padova, Italy. [email protected].
  • 26 Department of Medicine, University of Padova, Padova, Italy. [email protected].
  • 27 Institute of Oncology Research (IOR), Bellinzona, Switzerland. [email protected].
  • 28 Università della Svizzera italiana, Lugano, Switzerland. [email protected].
  • 29 Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland. [email protected].
  • 30 Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland. [email protected].
  • # Contributed equally.
PMID: 38951692 DOI: 10.1038/s43587-024-00663-7
Abstract

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

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