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Updated: Jun 22, 2025
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and
Sara Zumerle1,2, Miles Sarill1,3, Miriam Saponaro1,2,4
1Veneto Institute of Molecular Medicine, Padova, Italy.
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.
Insights
A Salvia haenkei extract (Haenkenium) extended lifespan and healthspan in mice by targeting cellular senescence. This botanical extract, containing luteolin, disrupted the p16-CDK6 interaction, a key aging pathway.
Area of Science:
- Gerontology
- Pharmacology
- Natural Products
Background:
- Cellular senescence, the accumulation of aging cells, drives age-related diseases.
- Botanical extracts offer potential therapeutic agents targeting senescence to improve healthspan.
- Salvia haenkei (Haenkenium) is a botanical extract rich in phytoconstituents.
Purpose of the Study:
- To investigate the effects of Haenkenium (HK) on lifespan and healthspan in aged mice.
- To determine if HK modulates cellular senescence and related markers.
- To identify active compounds in HK and elucidate their mechanism of action.
Main Methods:
- Daily oral administration of standardized Salvia haenkei extract (HK) to naturally aged mice.
- Assessment of lifespan, healthspan markers (inflammation, fibrosis, senescence), muscle strength, and fur thickness.
- Evaluation of HK's effect on doxorubicin-induced senescence using p16LUC reporter mice.
- Chemical profiling of HK by mass spectrometry and identification of luteolin.
- In vitro assays (SPR, iPLA) to investigate luteolin's interaction with p16-CDK6.
Main Results:
- HK administration significantly extended lifespan and improved healthspan in aged mice.
- HK treatment reduced age-induced inflammation, fibrosis, and senescence markers.
- HK improved physical parameters like muscle strength and fur thickness.
- HK attenuated doxorubicin-induced senescence in reporter mice.
- Luteolin was identified as the primary senomorphic flavonoid in HK.
- Luteolin was shown to disrupt the p16-CDK6 interaction.
Conclusions:
- Standardized Salvia haenkei extract (Haenkenium) promotes longevity and healthspan in mice.
- HK's beneficial effects are likely mediated by modulating cellular senescence.
- Disruption of the p16-CDK6 interaction by luteolin is a key mechanism underlying HK's senomorphic activity.
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