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Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.
Zumerle, Sara; Sarill, Miles; Saponaro, Miriam; Colucci, Manuel; Contu, Liliana; Lazzarini, Edoardo; Sartori, Roberta; Pezzini, Camilla; Rinaldi, Anna; Scanu, Anna; Sgrignani, Jacopo; Locatelli, Patrizia; Sabbadin, Marianna; Valdata, Aurora; Brina, Daniela; Giacomini, Isabella; Rizzo, Beatrice; Pierantoni, Alessandra; Sharifi, Saman; Bressan, Silvia; Altomare, Claudia; Goshovska, Yulia; Giraudo, Chiara; Luisetto, Roberto; Iaccarino, Luca; Torcasio, Cristina; Mosole, Simone; Pasquini, Emiliano; Rinaldi, Andrea; Pellegrini, Laura; Peron, Gregorio; Fassan, Matteo; Masiero, Stefano; Giori, Andrea Maria; Dall'Acqua, Stefano; Auwerx, Johan; Cippà, Pietro; Cavalli, Andrea; Bolis, Marco; Sandri, Marco; Barile, Lucio; Montopoli, Monica; Alimonti, Andrea.
Afiliación
  • Zumerle S; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Sarill M; Department of Medicine, University of Padova, Padova, Italy.
  • Saponaro M; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Colucci M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Contu L; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Lazzarini E; Department of Medicine, University of Padova, Padova, Italy.
  • Sartori R; Department of Urology and Pediatric Urology, University Medical Center Bonn (UKB), Bonn, Germany.
  • Pezzini C; Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Rinaldi A; Università della Svizzera italiana, Lugano, Switzerland.
  • Scanu A; Faculty of Biology and Medicine, University of Lausanne UNIL, Lausanne, Switzerland.
  • Sgrignani J; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Locatelli P; Department of Medicine, University of Padova, Padova, Italy.
  • Sabbadin M; Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • Valdata A; Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland.
  • Brina D; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Giacomini I; Department of Biomedical Sciences, University of Padova, Padova, Italy.
  • Rizzo B; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Pierantoni A; Department of Biomedical Sciences, University of Padova, Padova, Italy.
  • Sharifi S; Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.
  • Bressan S; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
  • Altomare C; Department of Neuroscience, Rehabilitation Unit, University of Padova, Padova, Italy.
  • Goshovska Y; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Giraudo C; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Luisetto R; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Iaccarino L; Department of Medicine, University of Padova, Padova, Italy.
  • Torcasio C; Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
  • Mosole S; Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Pasquini E; Università della Svizzera italiana, Lugano, Switzerland.
  • Rinaldi A; Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland.
  • Pellegrini L; Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Peron G; Università della Svizzera italiana, Lugano, Switzerland.
  • Fassan M; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Masiero S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Giori AM; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Dall'Acqua S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Auwerx J; Veneto Institute of Oncology IOV - IRCCS, Padova, Italy.
  • Cippà P; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Cavalli A; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Bolis M; Institute for Research on Cancer and Aging, Nice, France.
  • Sandri M; Veneto Institute of Molecular Medicine, Padova, Italy.
  • Barile L; Department of Medicine, University of Padova, Padova, Italy.
  • Montopoli M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Alimonti A; Veneto Institute of Molecular Medicine, Padova, Italy.
Nat Aging ; 4(9): 1231-1248, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38951692
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Extractos Vegetales / Senescencia Celular / Polifenoles / Longevidad Límite: Animals Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Extractos Vegetales / Senescencia Celular / Polifenoles / Longevidad Límite: Animals Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos