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

Details

Serval ID
serval:BIB_F01027CE166C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.
Journal
Nature aging
Author(s)
Zumerle S., Sarill M., Saponaro M., Colucci M., Contu L., Lazzarini E., Sartori R., Pezzini C., Rinaldi A., Scanu A., Sgrignani J., Locatelli P., Sabbadin M., Valdata A., Brina D., Giacomini I., Rizzo B., Pierantoni A., Sharifi S., Bressan S., Altomare C., Goshovska Y., Giraudo C., Luisetto R., Iaccarino L., Torcasio C., Mosole S., Pasquini E., Rinaldi A., Pellegrini L., Peron G., Fassan M., Masiero S., Giori A.M., Dall'Acqua S., Auwerx J., Cippà P., Cavalli A., Bolis M., Sandri M., Barile L., Montopoli M., Alimonti A.
ISSN
2662-8465 (Electronic)
ISSN-L
2662-8465
Publication state
Published
Issued date
09/2024
Peer-reviewed
Oui
Volume
4
Number
9
Pages
1231-1248
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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 p16 <sup>LUC</sup> 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.
Keywords
Animals, Longevity/drug effects, Plant Extracts/pharmacology, Mice, Cellular Senescence/drug effects, Polyphenols/pharmacology, Salvia/chemistry, Aging/drug effects, Doxorubicin/pharmacology, Cyclin-Dependent Kinase Inhibitor p16/metabolism, Cyclin-Dependent Kinase Inhibitor p16/genetics, Luteolin/pharmacology, Male
Pubmed
Web of science
Open Access
Yes
Create date
11/07/2024 15:43
Last modification date
21/09/2024 7:09
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