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

Autor: Zumerle S; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, University of Padova, Padova, Italy., Sarill M; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Saponaro M; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, University of Padova, Padova, Italy.; Department of Urology and Pediatric Urology, University Medical Center Bonn (UKB), Bonn, Germany., Colucci M; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland.; Faculty of Biology and Medicine, University of Lausanne UNIL, Lausanne, Switzerland., Contu L; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, University of Padova, Padova, Italy., Lazzarini E; Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland., Sartori R; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Biomedical Sciences, University of Padova, Padova, Italy., Pezzini C; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Biomedical Sciences, University of Padova, Padova, Italy., Rinaldi A; Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Scanu A; Department of Neuroscience, Rehabilitation Unit, University of Padova, Padova, Italy., Sgrignani J; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Locatelli P; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Sabbadin M; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, University of Padova, Padova, Italy.; Veneto Institute of Oncology IOV - IRCCS, Padova, Italy., Valdata A; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland.; Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland., Brina D; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Giacomini I; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Rizzo B; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.; Veneto Institute of Oncology IOV - IRCCS, Padova, Italy., Pierantoni A; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.; Institute for Research on Cancer and Aging, Nice, France., Sharifi S; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Medicine, University of Padova, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Bressan S; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Altomare C; Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland., Goshovska Y; Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland., Giraudo C; Department of Medicine, University of Padova, Padova, Italy.; Department of Cardiac, Thoracic, Vascular Sciences and Public Health - DCTV, University of Padova, Padova, Italy., Luisetto R; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy., Iaccarino L; Department of Medicine, University of Padova, Padova, Italy., Torcasio C; Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Mosole S; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Pasquini E; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Rinaldi A; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Pellegrini L; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Peron G; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Fassan M; Department of Medicine, University of Padova, Padova, Italy.; Veneto Institute of Oncology IOV - IRCCS, Padova, Italy., Masiero S; Department of Neuroscience, Rehabilitation Unit, University of Padova, Padova, Italy., Giori AM; R&D Department, IBSA Farmaceutici Italia, Lodi, Italy., Dall'Acqua S; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy., Auwerx J; Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Cippà P; Università della Svizzera italiana, Lugano, Switzerland.; Department of Medicine, Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.; Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland., Cavalli A; Università della Svizzera italiana, Lugano, Switzerland.; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Bolis M; Institute of Oncology Research (IOR), Bellinzona, Switzerland.; Università della Svizzera italiana, Lugano, Switzerland., Sandri M; Veneto Institute of Molecular Medicine, Padova, Italy.; Department of Biomedical Sciences, University of Padova, Padova, Italy., Barile L; Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.; Faculty of Biomedical Sciences, Euler Institute, Università della Svizzera Italiana, Lugano, Switzerland., Montopoli M; Veneto Institute of Molecular Medicine, Padova, Italy. monica.montopoli@unipd.it.; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy. monica.montopoli@unipd.it., Alimonti A; Veneto Institute of Molecular Medicine, Padova, Italy. andrea.alimonti@ior.usi.ch.; Department of Medicine, University of Padova, Padova, Italy. andrea.alimonti@ior.usi.ch.; Institute of Oncology Research (IOR), Bellinzona, Switzerland. andrea.alimonti@ior.usi.ch.; Università della Svizzera italiana, Lugano, Switzerland. andrea.alimonti@ior.usi.ch.; Department of Health Sciences and Technology (D-HEST), ETH Zurich, Zurich, Switzerland. andrea.alimonti@ior.usi.ch.; Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland. andrea.alimonti@ior.usi.ch.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2024 Sep; Vol. 4 (9), pp. 1231-1248. Date of Electronic Publication: 2024 Jul 01.
DOI: 10.1038/s43587-024-00663-7
Abstrakt: 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 p16 LUC 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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