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
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
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