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Naringenin is a Senotherapeutic that Enhances Neurogenesis in Mice

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#1 reason

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Posted 25 September 2020 - 10:22 AM

Researchers here evaluate the flavonoid naringenin for its ability to dampen the inflammatory signaling of senescent neural cells, particularly levels of TNF-α, and increase neurogenesis in mice. This increased neurogenesis is likely a result of reduced inflammation in brain tissue, but possibly due to other, distinct mechanisms. Neurogenesis is the name given to the generation of new neurons in the brain, and their integration into existing neural circuits. Evidence suggests that increased neurogenesis is a good thing at any age, improving cognitive function and making the brain more resilient to injury. Now that the research community is paying attention to senescent cells and their signaling in the context of aging, we'll no doubt see a great many compounds classified or reclassified as senotherapeutics in the years ahead.

The use of metabolomic analysis to investigate the specific composition of Ribes meyeri anthocyanins revealed that naringenin (Nar) may be an important flavonoid metabolite. Nar has previously been reported to ameliorate myocardial cell senescence, improve the metabolic capacity of the intestinal tract, and exert anti-inflammatory and anti-cancer effects. However, the effects of Nar on neural stem cells (NSCs) during aging remains unknown.

To explore the anti-aging effects of R. meyeri anthocyanins, we conducted further studies using Nar. Treatment with 6.8 μg/mL Nar increased cell viability, reduced P16ink4a gene expression, lengthened telomeres, and promoted mouse NSC differentiation into neurons in vitro. To further assess the effects of Nar on cell proliferation, we performed immunofluorescence studies. Results indicated that Nar treatment increased both the number of Ki67-positive cells and the proportion of MAP2-positive cells, suggesting that Nar may promote neurogenesis.

Furthermore, the effects of Nar on learning and memory were also evaluated in aging mice. Morris water maze test results consistently demonstrated that Nar treatment enhances spatial learning in aging mice. Interestingly, RNA-seq analysis revealed that Nar may affect senescence via the TNF signaling pathway, especially by downregulating TNF-α expression in the blood of aging mice. ELISA assays also indicated that Nar treatment reduced plasma TNF-α levels compared with control aging mice. TNF-α is a key factor in the TNF signaling pathway and is closely related to cognitive aging. Its functions include the promotion of pathological changes in hippocampal synapses and the inhibition of precursor cell proliferation. Altered TNF levels are associated with cognitive impairment in depression, schizophrenia, bipolar disorder, and Alzheimer's disease. More specifically, TNF-α is upregulated in patients with Alzheimer's disease.

In summary, our study demonstrates that R. meyeri anthocyanins improve the effects of aging in NSCs via Nar, which downregulates TNF-α levels in vivo and improves cognition in aging mice. Collectively, our findings provide a novel strategy for the development of clinical treatments, aimed at greater realization of the medicinal value of R. meyeri anthocyanins.

Link: https://doi.org/10.18632/aging.103955

View the full article at FightAging

#2 Mind

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Posted 25 September 2020 - 02:04 PM

Yet another antioxidant, antimicrobial, anti-inflammatory, somewhat senolytic flavanoid found in (brightly colored) fruits and vegetables.


One would tend to think vegans and vegetarians would live far past anyone on the planet. I wonder if the excess sugar/calorie content of many fruits and vegetables is why the effect is not too pronounced. Or perhaps that vegans and vegetarians eat too much grain.

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#3 Harkijn

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Posted 25 September 2020 - 03:44 PM

No, complex carbs feed our microbiome so we are okay there. We vegetarians however run the risk of eating too little Omega-3 and vitamin B12. 


You mention polyphenols: many of them inhibit iron absorption from food. Many posters on Longecity will probably eat low meat diets and add berries to many meals: blueberries, blackberries, raspberries and  also supplement with resveratrol or fisetin. I recently found out the hard way that you can feel healthy but still be very low in Hemoglobin, Transferrin etc. For me, and perhap more vegetarians it is much better to eat your berries and supps well away from meals that contain only plantbased iron.

Edited by Harkijn, 25 September 2020 - 03:45 PM.

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