Not only does removing senescent cells reduce damage and increase resilience of non-senescent cells, REDUCING the senescent associated phenotype or the expression of destructive enzymes works to improve non- senescent cell function and resilience.
This is one of many studies showing that phytochemicals, in this case Apigenin, REDUCE the SASP phenotype and improve tissue function and resilience.
Sulforaphane shows similar affects.
Hydrogen rich water shows similar effects.
Wheat germ/spermidine shows similar effects.
Melatonin shows similar effects.
All through different entry points but all can be blocked by autophagy blockade.
Which pathway is the driver?
Nrf2 is the driver.
When autophagy is increased genes such as BDNF and other "starvation gene set" are increased by upregulated transcription, and perhaps by turning these genes back on through the combination of HDAC inhibition and de-methylation of cytosine gene promoter sites. This reverses oxidative stress and decreased energy related epigenic switched off genes.
The anti-aging anti inflammatory Nrf2 pathway suppresses p38-MAPK, and NF-κB.
All of the above activate Nrf2 and suppress downstream p38-MAPK, and NF-κB.
Activate the Nrf2 pathway reduce SASP and increase resilience through appropriate autophagy control and signaling.
One either gains and maintains resilience via autophagy signaling and action OR one loses resilience and drift to senescent somatic and stem cells. The latter leads to degenerative changes, senescent cells or the consequences of senescence- loss of function or malignant transformation.
Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells
Apigenin (4′,5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells—stressed cells that accumulate with age in mammals—display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelial-mesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.
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