Naringenin — an Anti-Aging Compound Found in Grapefruit — Increases Neural Stem Cell Proliferation, Improves Cognition, and Decreases Markers of Senesence

by Nils Osmar

The information in this article is not intended as, and should not be taken as, medical advice. Interventions like exercising, dietary changes, and taking medications and supplements can have both benefits and side effects, Please consult with a medical professional about any medical concerns.  See full Medical Disclaimer

A 2020 study authored by researchers at Tongji University in Shanghai and Shihezi University in Shihezi City, and published in Aging, found that anthocyanins extracted from Ribes meyeri — a plant in the currant/gooseberry family — have profound anti-aging effects on the brain, specifically on neural stem cells (NSCs) and cognitive function in aging mice.

Both In Vitro and In Vivo Studies

In cell culture (in vitro): After treatment with R. meyeri anthocyanins, neural stem cell proliferation accelerated, senescence markers decreased, and the aging-associated gene P16ink4a was downregulated.

The treated aged NSCs also showed reduced reactive oxygen species (ROS), lengthened telomeres, and greater capacity to differentiate into neurons — essentially, many hallmarks of cellular aging were reversed or improved.

In living mice (in vivo): When 12-month-old aging mice were given the extract orally for two months, they performed significantly better on the Morris water maze test — finding a hidden platform faster and more efficiently — indicating improved spatial memory and learning. Importantly, their swimming speed didn’t change, so this wasn’t just a motor improvement; it was genuinely cognitive.

The key ingredient — Naringenin (Nar):

Through metabolomic analysis, the researchers identified naringenin as a particularly important flavonoid within the anthocyanin extract. When tested on its own, Nar reproduced many of the same anti-aging effects: reversing senescence in aged NSCs, promoting neurogenesis, and improving cognition in aging mice.

How It Works

TNF-α is a pro-inflammatory cytokine already known to be associated with cognitive impairment, hippocampal synaptic pathology, and conditions like Alzheimer’s disease.

RNA sequencing of blood from the treated mice found that the TNF signaling pathway was significantly downregulated. ELISA assays confirmed that Nar treatment reduced plasma TNF-α protein levels, and the researchers also showed that p16ink4a expression was reduced in the hippocampus.

Note: This was a preclinical study in mice, and has not been confirmed in humans. But it adds to a growing body of work on flavonoids and neuroinflammation in aging.

From the Study:

Cognitive levels decline with aging, and anti-aging treatments can improve cognitive levels [11, 28]. To verify the anti-aging effects of Nar in vivo, we injected 20 mg/kg Nar into aging C57BL/6 mice (12 months old) through the tail vein. The MWM test was used to examine the spatial memory and cognitive abilities of the mice. Over 5 days of repeated training, the time taken for Nar-treated aging mice to find the platform gradually decreased compared with the control group (Figure 4A).

The test results revealed that the time taken to first reach the platform was reduced (Figure 4B), while the time spent in the platform zone was increased (Figure 4C). Furthermore, Nar-treated aging mice were observed within the platform zone at a higher frequency than the control group (Figure 4D). Together, these results suggest that Nar can improve spatial memory and cognitive abilities in aging mice.

What It Means

The authors propose that R. meyeri anthocyanins — working primarily through naringenin — combat brain aging by suppressing the inflammatory TNF-α signaling pathway, which in turn supports neural stem cell proliferation, promotes the generation of new neurons, and improves cognitive function in aging mice.

The study found that the specific mechanism driving the anti-aging effect was naringenin acting on the TNF-α signaling pathway.

Foods Rich in Naringenin

As I mentioned above, the naringenin used in the study was extracted from the Ribes meyeri plant. But interestingly, this compound is also, and predominantly, found in citrus fruits, especially grapefruit, and in smaller quantities in tomatoes, oranges, and bergamot.

According to the USDA’s flavonoid database, citrus fruits are the only foods that contain flavanones like naringenin in significant quantities.

Not All Anthocyanins Are the Same

I eat wild blueberries every day, so I checked to see whether this might be providing me with some naringenin. Blueberries do have several other beneficial compounds (delphinidin, cyanidin, malvidin, etc.) which also appear to be highly beneficial to cognition. But they have very little of this one.

R. meyeri‘s benefits appear to get their edge specifically from naringenin’s targeted suppression of TNF-α. To support this particular pathway, grapefruit or citrus would be a logical addition to our diets.

What I’m Doing

• While I am aware of the need for human studies, I find this animal study convincing enough that I have recently added grapefruit back into my diet.
• I am currently eating about 1/4 grapefruit per day.
• I’m also continuing to eat a half cup to a cup of wild blueberries daily.
• I find that fruit and berries increase my blood sugar and A1C. To avoid this, I eat small quantities with meals instead of eating one big bowl of grapefruit and blueberries together. I spread out eating a full grapefruit over several days’ time.
• Note that naringenin is also available as a supplement.

Caveats and Side Effects

• The naringenin in the study was delivered by injection. We don’t know whether eating foods rich in it will have identical benefits.
• Evidence of neural improvement in mice is not necessarily proof of the same phenomenon in humans.
• Human studies are needed to prove that similar benefits would be obtained in humans obtaining the compound orally.
• Anytime you take a supplement, it’s wise to do some research into both. It’s possible benefits, and side effects. Here are some: “Naringin is a natural citrus flavonoid generally considered safe, but high doses or excessive grapefruit consumption can cause side effects such as gastrointestinal discomfort, blood pressure drops, or enhanced bleeding risks. It interacts with medication metabolism (similar to grapefruit juice) and can have anti-estrogenic effects at high levels”
• Full study: Anti-aging effects of Ribes meyeri anthocyanins on neural stem cells and aging mice

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More from Nils Osmar

• Anti-Aging Youtube channel Pathways to Longevity
• Anti-Aging Facebook group: Anti-Aging and Life Extension
• Rekindle School classes in Seattle: Rekindl.e School
• My personal website: My articles, art and more: Nilsosmar.com
• Exploring possible consciousness in Claude.AI and other LLMs: AI Consciousness
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