Aging & Longevity

Scientists Successfully Increase Lifespan and Delay Brain Aging with New Prebiotic

Researchers show that the dietary prebiotic neagarotetraose (NAT) - a compound that alters the microbiome - prolongs lifespan and mitigates age-related brain damage in mice by regulating the gut.

By Dylan G. Arrazati

Key Points:

  • 12 months of treatment with NAT increases survival by 33.3%.
  • Treatment with NAT boosts neuron survival in naturally aging mice and mitigates Alzheimer’s (AD) pathology in mice modeling AD. 
  • NAT improves gut health by increasing the abundance of short-chain fatty acids.

Our gut microbiome – an internal hub housing trillions of nutrient-boosting microorganisms, including bacteria and other microbes – is emerging as a central modulator of health and wellness. Studies have linked poor gut health to a myriad of harmful aged-related conditions like diabetes, cancer, and central nervous system complications that affect the brain. Now, compounds known as prebiotics, which nourish the microbiome, are currently under investigation for their potential role in longevity and ability to mitigate age-related health risks tied to brain dysfunction. 

In a new study published in the Journal of Advanced Research,  scientists found that supplementing naturally aged mice with the prebiotic NAT increased lifespan by 33.3% and protected against neuron deterioration. Jiang and colleagues also showed that treating mice modeling Alzheimer’s (AD) with NAT improved cognitive function and alleviated multiple AD features.  Moreover, following supplementation, the guts of naturally aged mice and AD mice exhibited higher levels of short-chain fatty acids (SCFAs), which are vital to regulating inflammation in the gut and brain.  

How the Gut Can Influence the Brain 

Studies have established the intimate relationship between gut health and brain function, showing that our bodies utilize a pathway called the gut-brain axis to facilitate communication required for several intestinal and cognitive functions. As we age, we become increasingly susceptible to gut-brain axis inflammation, a known driver of age-related neuron degeneration and reduced gut-barrier protection. However, researchers have shown that SCFA’s heavily regulate gut-brain axis inflammation, preserving gut health and function. Given that gut SCFAs decrease with age, scientists have searched for interventions capable of restoring healthy SCFAs.

NAT Increases Lifespan, Protects Neurons, and Improves Gut Health

Prebiotics are currently in the spotlight for gut and brain health interventions, as they hold potent anti-inflammatory and anti-oxidative properties. What’s more, prebiotics like NAT have been shown to prolong the lifespan of worms and increase SCFAs in mice. However, whether NAT’s ability to replenish SCFAs can lead to increased lifespan and reduced neurodegeneration remains unclear. 

In the present study, Jiang and colleagues supplemented naturally aged (8-month-old) mice with NAT for 12 months and monitored the effects on lifespan, neuron survival, and SCFA abundance. The investigators also supplemented one group of mice with metformin, which has been shown to boost microbiome health, increase SCFAs in humans, and increase rodent lifespan.

Compared to untreated mice,  those supplemented with NAT lived 33.3% longer, and those supplemented with metformin lived 41.7% longer.  Furthermore, NAT and metformin treatment  significantly increased neuron survival in the hippocampus –  the brain region responsible for learning and memory. Notably, untreated mice had drastically lower levels of SCFAs than mice treated with NAT or metformin, potentially explaining the observed benefits on neuron survival following treatment. Collectively, the findings suggest that NAT exerts pro-longevity effects by enhancing gut and brain health. 

(Jiang et al., 2023 | Journal of Advanced Research) NAT increases lifespan, neuron survival, and SCFAs. (Left) Aged mice treated with NAT (red) live longer than untreated mice (black) but shorter than those treated with metformin (green). (Middle/Right) NAT-treated mice (NAT) have more neurons and different species of SCFAs than untreated mice (NA) but fewer neurons and SCFAs than metformin-treated mice (MET).

NAT Protects Against Alzheimer’s Disease

After demonstrating NATs ability to delay brain aging via the microbiome, the investigators sought to determine whether NAT could be used to protect against age-related neurodegenerative disorders, specifically AD, through gut-brain axis regulation. To assess NATs effects on brain health in AD mice, Jiang and colleagues conducted cognitive testing and quantified the levels of amyloid beta (Aβ), a toxic protein associated with  AD pathology. They also repeated SCFA calculations to highlight the potential relationship between gut health and AD. 

The research team evaluated spatial memory by employing the Morris Water Maze test, where mice were trained to locate a hidden platform in a pool of water. The results showed that AD mice treated with NAT for 3 months spent 30.1% less time finding the hidden platform than untreated AD mice. Additionally, untreated AD mice allocated the least amount of time exploring the region with the hidden platform, indicating impaired memory. Accordingly, untreated AD mice also displayed the highest levels of Aβ and the least amount of SCFAs, suggesting that NAT influences AD pathology through gut SCFA regulation. 

(Jiang et al., 2023 | Journal of Advanced Research) NAT mitigates Alzheimer’s pathology and increases SCFAs. (Left) NAT-treated AD mice (NAT) spent more time in the target quadrant than untreated AD mice (AD), indicating improved memory. AD mice treated with NAT have significantly less Aβ (Middle) in two brain regions and higher levels of SCFAs (Right) than untreated AD mice.

Trust Your Gut For Healthier Aging

The study’s findings support the growing body of evidence demonstrating the intricate role of the gut microbiome in regulating aging and age-related diseases.  Providing our guts with the right tools, such as prebiotics like NAT, allow our bodies to harness vital nutrients critical to survival and cognitive function. Conversely, consuming high amounts of processed foods can reduce the diversity of beneficial bacteria and create an imbalanced microbiome, triggering inflammation and further driving metabolic disorders. So, in the long run, it may be worth trusting the signals our guts send to us, as it can potentially lead to healthier aging.

Model & Dosage

Model: C57BL/6J mice (male, 8 months old); APP/PS1 double transgenic (APPswe/PSEN1dE9) mice with five familial Alzheimer’s diseases (5 FAD); and littermate wild-type C57BL/6J mice (male, 8 months old) 

Dosage: neoagarotetraose (NAT) 1000 mg/kg*bw/d via drinking water


Li, S. Yang, X. Liu et al., Dietary neoagarotetraose extends lifespan and impedes brain aging in mice via regulation of microbiotagut-brain axis, Journal of Advanced Research,

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