Eating for an Aging Brain: How Nutraceuticals and Functional Foods Target Cellular Aging

An international team of researchers has published a review in Nutrients on how nutraceuticals (bioactive substances from food) and functional foods can reduce cellular senescence, a key mechanism of aging, and thereby potentially slow the progression of Alzheimer's and Parkinson's diseases. The authors bring together data on antioxidant vitamins, polyphenols, spices, fiber, probiotics/prebiotics, and polyunsaturated fatty acids, describing how they reduce oxidative stress, tune gene expression, and dampen the inflammatory "secretory" phenotype of senescent cells (SASP). Importantly, direct clinical evidence for reducing the number of senescent cells is still limited - this area is just gaining momentum.

Background of the study

Brain aging and neurodegenerative diseases (Alzheimer's, Parkinson's) increasingly determine the duration of healthy life. One of the key mechanisms is cellular senescence: cells enter a persistent division arrest and secrete a pro-inflammatory "set" of factors (SASP), which disrupts the work of neighboring cells and tissues, including neuroglia. Senescence inhibition and/or SASP weakening are now considered promising targets for the prevention of cognitive decline.

Against this backdrop, there is growing interest in nutraceuticals and functional foods as gentle, long-term modulators of aging pathways: antioxidants, polyphenols, omega-3 PUFAs, components of the Mediterranean diet, fiber/prebiotics, etc. They target nodes of aging biology - oxidative stress, mitochondrial dysfunction, autophagy, Nrf2/AMPK/SIRT signaling pathways - and potentially reduce SASP "inflammation." A review in Nutrients systematizes this line of evidence and discusses how food molecules can slow cellular aging and thereby indirectly reduce the risk of neurodegeneration.

In parallel, the field of senotherapy is being formed: from “senostatics” (restrain the aging phenotype) to “senolytics” (selectively remove senescent cells). There are already clinical signals - for example, the combination of dasatinib + quercetin reduced the burden of senescent cells in humans in small trials, which supports the concept itself. However, nutraceuticals in this paradigm still need standardization of doses/formulations and validated biomarkers of response in humans.

It is important to remember the limits of evidence: for many compounds, data are strong in cell and animal models but limited in RCTs in humans; plus the effect is often dose- and context-dependent (“hormesis”). Therefore, the authors of the review suggest considering nutraceuticals not in isolation, but as part of a lifestyle (for example, the Mediterranean diet), for which associations have accumulated with “slower” aging biology and less inflammation. The task in the coming years is to transfer the mechanistics to the clinic: markers of senescence in humans, standardized protocols and long-term studies of cognitive outcomes.

Why is senescence important at all?

With age, tissues accumulate cells that have entered a persistent division arrest. They do not divide, but actively secrete inflammatory molecules, enzymes, and signals that change their neighbors and microenvironment. In the brain, not only neurons can become senescent, but also astrocytes, oligodendrocytes, and microglia. Such “senescent” microglia are especially harmful: they add fuel to the fire of chronic neuroinflammation associated with cognitive decline and protein pathologies (Aβ, tau, α-synuclein) in dementia and Parkinson's. Weakening senescence and/or SASP is considered a new target for the prevention and accompanying treatment of neurodegeneration.

Nutraceuticals as Senotherapy: What Exactly They Do

The general theme of the review is as follows: different classes of food molecules hit common “nodes” of aging - excess reactive oxygen species, mitochondrial dysfunction, autophagy failure, nutrition/signaling imbalance (mTOR, AMPK), epigenetics and SASP “fire”. A separate line is the “hormesis” effect: low doses of a number of compounds turn on stress resistance pathways (e.g. Nrf2, SIRT1/3), while too high doses can be useless or even harmful. In parallel, the authors remind: moderate calorie restriction and the Mediterranean diet are rich in the same “microdoses” of phytonutrients and are associated with a better cognitive trajectory and “slower” signs of cellular aging.

Who's on the list of contenders (and at what expense)

The review contains a large summary table of substances and models - from cellular experiments to animals and the first clinical studies. Below are the most discussed groups and their supposed targets.

• Antioxidant vitamins (C, E, A, B9/folate and B12). Neuroprotective and anti-senescence effects have been shown in models: reduction of ROS, support of synaptic plasticity, effects on telomeres, reduction of senescence markers in astrocytes with B12 deficiency; for vitamin E, effects on ERK/PI3K/AKT and motility in PD models. There are clinical associations (e.g. folates in mild cognitive impairment), but the general conclusion is that senescence markers are needed in humans.
• Polyphenols, terpenes and terpenoids.
  • Quercetin is a senostatic and even senolytic in some model systems; in combination with dasatinib (D+Q), it cleared oligodendrocyte progenitors in an AD model and ameliorated inflammation and cognitive deficits.
  • Resveratrol - activates SIRT1/AMPK, supports mitochondria and autophagy at low doses; higher doses in animal models sometimes produced opposite effects (an example of dose-dependent "hormesis").
  • Oleuropein (olive oil) - prevents the aggregation of α-synuclein, activates antioxidant transcription factors.
  • Fisetin - improved cognitive tests and was noted as a promising senolytic.
  • Green tea (EGCG) and ginkgolides - evidence for reducing lipid peroxidation, supporting antioxidant enzymes and protecting dopaminergic neurons.
• Spices as a "micro first aid kit".
  • Curcumin - adjusts Keap1/Nrf2/ARE, reduces microgliosis, helps Aβ-clarification by macrophages; simultaneously affects BACE1 and APP-processing; direct anti-senescence effects (telomerase, SIRT-pathways) have also been noted.
  • Piperine (black pepper) - reduced MPTP-induced motility disorders and inflammation, increased Bcl-2/Bax.
  • Cinnamon/cinnamaldehyde and cardamom - in models reduced Aβ aggregation and toxicity, increased BDNF, and inhibited α-synuclein oligomers.
• Fiber, prebiotics, and probiotics. A high-fiber diet and short-chain fatty acids (butyrate, etc.) affect the gut-brain axis, reduce neuroinflammation, help microglia “calm down,” and in AD models, slow cognitive decline and modify the microglia transcriptome. Probiotics have been shown to reduce markers of inflammation and oxidative stress and protect dopaminergic neurons.
• Omega-3 PUFAs (DHA/EPA): Associated with lower risk of PD, reduced brain amyloid, modulation of tau pathology, and improved cognitive performance; mechanisms include membrane softening, antioxidant and anti-inflammatory effects, and support for neuroplasticity.

What Holistic Diets Show

The authors highlight two lifestyle strategies that “support” the same pathways as individual molecules. First, moderate calorie restriction: in experiments, it reduces molecular markers of senescence, improves mitochondrial function and neuroplasticity; in humans, moderate calorie restriction is associated with improved biomarkers of biological age (without obesity). Second, the Mediterranean diet: rich in vegetables/fruits/whole grains/fish and olive oil, it is associated with lower inflammation, better endothelial function, fewer signs of cellular stress and - in some studies - a “shorter list” of endothelial cells with signs of senescence and an altered microRNA profile.

Important Disclaimers

Despite the rich “biology,” the field is extremely young. The challenges are bioavailability (not everything that works in a petri dish makes it to the brain), dosage and “hormesis” (what’s beneficial in microdoses may not work in larger doses), heterogeneity in supplement and diet formulations, age-related changes in pharmacokinetics, and a lack of clinical studies with validated biomarkers of senescence. The authors call for mechanistic and clinical work, for the development of delivery systems, and for assessing the effects of nutraceuticals within diets like the Mediterranean, rather than in isolation from the nutritional context.

What this could mean for your plate right now

This is a journalistic summary of a scientific review, not a medical recommendation. But if you translate the trends into the language of everyday food, the "direction of movement" looks like this:

• Make a Mediterranean diet: more vegetables/fruits/legumes/nuts/whole grains; fish 1-2 times a week; the main fatty food is extra virgin olive oil.
• Give space to spices: turmeric, black pepper (piperine), cinnamon, cardamom - regularly, but in culinary, not pharmacological doses.
• Maintain fiber and fermented foods (yogurt/kefir/fermented milk with live cultures) - for the sake of short-chain fatty acids and “quiet” microglia.
• Be careful with supplements: many effects were obtained in preclinical models; doses and forms (for example, resveratrol, ginkgo, etc.) should only be discussed with a doctor, especially in case of chronic diseases and taking medications.

Conclusion

The review paints a compelling picture: Diet is not just a “fuel” but a regulator of cellular aging. Nutraceuticals from “regular” foods target nodes in the biology of aging—from mitochondria to autophagy to SASP—and together can mitigate age-related cellular and neuronal stress. But to translate this biology into therapy, science needs biomarkers of senescence in humans, well-designed clinical trials, and attention to the dose, form, and context of the holistic diet. Until then, a sensible strategy is to eat in ways that provide daily “microsignals” of protection (vegetables, berries, EVOO, spices, fish, fiber, and fermented foods)—which is what the best body of evidence to date shows.

Review source: Nutrients 2025, 17, 1837 - The Role of Nutraceuticals and Functional Foods in Mitigating Cellular Senescence… (Ristori et al.). https://doi.org/10.3390/nu17111837