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

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

PROVIDER: PRJNA1105119 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28817027.fastq.gz	Fastqsanger.gz
	SRR28817028.fastq.gz	Fastqsanger.gz
	SRR28817029.fastq.gz	Fastqsanger.gz
	SRR28817030.fastq.gz	Fastqsanger.gz
	SRR28817031.fastq.gz	Fastqsanger.gz

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

Project description:The accumulation of senescent cells within tissues contributes to age-related diseases through the senescence-associated secretory phenotype (SASP). To fight senescence and maintain a healthy tissue microenvironment, the quest for longevity-promoting compounds has resulted in promising discoveries from botanical sources. Here we show that daily administration with a low dose of Haenkenium (HK), a standardized extract of Salvia haenkei, extended the lifespan and healthspan of aged C57BL/6 mice by delaying senescence and consequently ameliorating systemic inflammation and fibrosis markers in multiple tissues including skin, muscle, cartilage, and kidney. Additionally, treated aged mice displayed increased muscle strength, vitality, and thicker fur coverage than age-matched controls. Notably, HK treatment also effectively reduced doxorubicin (Doxo)-induced senescence in p16LUC reporter mice and protected against Doxo-induced cardiotoxicity. The composition of HK was analyzed by UPLC-QTOF-MS, which revealed multiple polyphenols that were then screened for their putative anti-senescence activity in vitro. Among these, luteolin, luteolin- 7-O-glucuronide and 3,4-dicaffeoylquinic were identified as HK-derived constituents with comparable activity to HK. Mechanistically, we report that luteolin could disrupt the p16-CDK6 interaction, which was validated by surface plasmon resonance (SPR) and by in situ proximity ligation assay in vitro. Our findings suggest that phytoconstituents such as luteolin can alter the senescence phenotype by disrupting the activity of p16 which subsequently is associated with improved longevity in mice.

2024-05-01 | GSE266005 | GEO

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

Project description: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.

| S-EPMC11408255 | biostudies-literature

Diet supplemented with polyphenol- and glucuronoxylan-rich fiber extract regulates colonic barrier function and cell proliferation in healthy rats

Project description:A diet rich in dietary fiber and polyphenols supports the normal intestinal barrier function crucial for intestinal and overall health. Birch wood-derived fiber containing glucuronoxylans (GX)- and polyphenols have the potential in multiple food technological applications and have favorable effects on gut microbiota and colonic metabolism. However, their impact on intestinal barrier function is unknown. To elucidate their potential as new intestinal health-supporting food ingredients, we investigated the effect of GX- and polyphenol-rich extract (GXpoly ) and highly purified GX-rich extract (pureGX) on the gene expression of the colon mucosa.

2023-12-01 | GSE230139 | GEO

Ginkgolide B increase healthspan and lifespan of female mice

Project description:Various anti-aging interventions exhibit potential in extending lifespan, yet most of these interventions are inefficacy or even have deleterious effects on healthspan. Ginkgolide B (GB) is a Ginkgo biloba-derived small molecule that reduces aging-related morbidities; however, the effects of GB on healthspan and longevity remain elusive. Here, we report that continuous oral GB administration in mice starting at 20 months extended their lifespan by 20% and reduced tumour incidence. Besides, GB administration significantly improved healthspan evidenced by enhancement in muscle quality, physical performance, grip strength, metabolism, frailty index, systemic inflammation, and senescence. Moreover, GB administration ameliorated aging-related pathologies without any apparent adverse effects. Single-nucleus RNA sequencing (snRNA-seq) revealed that GB improved aging-associated abnormal cell-type composition, intracellular signalling pathways, and cell-cell communication in skeletal muscles. GB also reduced the levels of aging-induced novel Runx1+ type 2B myonuclei, which are associated with apoptotic burden and aging-related signatures. Runx1 derived senescence, as shown by gain- and loss-of-function assays. Together, a new function of GB in extending the healthspan in aging is identified, which contributes to lifespan extension. The senomorphic effects of GB on the multifactorial aging process may provide new prospects for achieving healthy aging and longevity extension.

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Comprehensive proteomic study of the antiproliferative activity of a polyphenol-enriched rosemary extract on colon cancer cells using nano-liquid chromatography-Orbitrap MS/MS

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2016-06-08 | PXD003623 | Pride

Diet supplemented with polyphenol- and glucuronoxylan-rich fiber extract regulates colonic barrier function and cell proliferation in healthy rats

Project description:Diet supplemented with polyphenol- and glucuronoxylan-rich fiber extract regulates colonic barrier function and cell proliferation in healthy rats

| PRJNA957722 | ENA

Ellagic Acid Enhances Longevity and Healthspan in Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway

Project description:The role of ellagic acid (EA), a natural antioxidant, in regulating anti-aging and its underlying mechanisms remains unclear. In this study, we investigated the anti-aging effects and molecular mechanisms of EA in Caenorhabditis elegans (C. elegans). Our results demonstrate that EA extends the lifespan of C. elegans, enhances motility, reduces lipofuscin accumulation, and improves overall healthspan. Additionally, EA reduces reactive oxygen species (ROS) accumulation in C. elegans under conditions of heat and oxidative stress. The insulin/IGF-1 signaling (IIS) pathway, a key regulator of longevity and stress resistance in C. elegans, was found to mediate EA's effects. EA treatment did not extend the lifespan of mutants defective in daf-2, daf-16, hsf-1, hlh-30, and skn-1, confirming that EA’s lifespan-extending effect operates through the IIS pathway. Furthermore, EA treatment increased the expression of stress response genes downstream of the IIS pathway. Based on RNA sequencing data, we further explored the molecular mechanisms and potential regulatory roles of EA in anti-aging.

2025-05-10 | GSE295741 | GEO

Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan.

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Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

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