• Aged mice supplemented with lion’s mane extract (He2) exhibit improved memory. 
  • Treatment with He2 decreases markers of inflammation and oxidative stress in the hippocampus – the brain structure responsible for learning and memory. 
  • He2 contains high concentrations of the powerful antioxidant ergothioneine (ERGO), which has been previously shown to exert neuroprotective effects.

Medicinal mushrooms have taken the health and wellness industry by storm, trending all over media outlets as the latest superfood. One particular mushroom in the spotlight of scientific research is lion’s mane, known to contain the widely touted “longevity vitamin” ergothioneine (ERGO).  Previous research shows that ERGO holds anti-oxidative and inflammatory properties that contribute to improved physical performance and neuroprotection. Now, researchers are further exploring ERGO’s effect on cognitive decline, a widespread issue of brain aging. 

In an article published in the journal Biology, Rossi and colleagues from the University of Pavia show that supplementing aged mice with a lion’s mane extract (He2) containing pure ERGO improves recognition memory, a cognitive function that deteriorates with age. What’s more, the investigators demonstrate that He2 treatment successfully reduces markers of inflammation and oxidative stress in the hippocampus.

He2 Enhances Cognitive Function 

Our hippocampus is the seat of knowledge retention and recollection, two key components that support recognition memory. Aging ultimately compromises these features, increasing susceptibility to neurodegenerative diseases like Alzheimer’s. Thus, finding ways to preserve knowledge and recollection is crucial to limiting cognitive impairment. With this in mind, Rossi and colleagues examined He2’s effect on recognition memory in naturally aging mice by conducting an array of spontaneous behavioral tests, which produced frailty index scores indicative of memory deterioration.

The behavioral knowledge tests showed that treating 15-month-old mice, which translates to 51 human years, with He2 via drinking water for eight months preserves knowledge, with aged treated mice exhibiting frailty scores similar to those in untreated young mice. Furthermore, the recollection behavioral tests demonstrated that treatment significantly boosts recollection. Notably, aged treated mice displayed frailty index scores lower than untreated young mice, suggesting a gain of function in the recollection component of memory. These findings indicate that He2 exerts preventative and neuroprotective effects on the aging brain. 

(Rossi et al., 2023 | Biology) He2 improves knowledge and recollection. Knowledge (left) and recollection (right) frailty index (FI) scores are lower in aged mice treated with He2 (green) than in untreated mice (red). Lower FI scores indicate improved cognitive function. T values indicate the point in time when the investigators took measurements. i.e. T0 = 11 months and T3 = 23 months. 

He2 Attenuates Inflammation and Oxidative Stress

Two primary drivers of brain aging and neurodegeneration are inflammation and oxidative stress. Studies have tied inflammation to brain senescence, a hallmark of brain aging stemming from senescent cells – aged dormant cells that trigger systemic inflammation and organ deterioration. Surmounting evidence also shows that oxidative stress plays a harmful role in impaired cognition and locomotor decline upon aging. Given that inflammation and oxidative stress severely affect brain health, scientists are continually searching for effective therapeutic interventions. 

To determine whether He2 attenuates inflammation and quenches oxidative stress, Rossi and colleagues examined multiple markers of both parameters in the hippocampus of aged treated mice. The results showed that He2-treated mice exhibited significantly lower levels of molecules (IL6 and TGFβ1) known to drive inflammatory diseases. Additionally, there was significantly less activity of oxidative stress-inducing compounds (NRF2, COX2) following treatment. Interestingly, COX2 inhibition has been previously shown to exert neuroprotective effects, further highlighting He2’s potential to treat neurological decline. Overall, the findings indicate that He2 holds nootropic (brain-boosting) properties that can potentially delay brain aging. 

(Rossi et al., 2023 | Biology) He2 lowers markers of inflammation (IL6 and TGFβ1) and oxidative stress (NRF2, COX2) . Aged mice treated with He2 (blue) have significantly lower levels of IL6, TGFβ1, NRF2, and COX2 than untreated mice (green) in two subregions of the hippocampus: DG and CA1. 

Medicinal Mushroom’s Role in Longevity

Two crucial bodily functions that dwindle with age are cognition and physical performance, both of which drastically exacerbate overall frailty and lead to decreased independence. Thus, researchers have honed in on therapies that target inflammation and oxidative stress, as these two cellular states have strong ties to neurodegenerative diseases and locomotor decline. Now, the findings of this study and previous experiments suggest that medicinal mushroom extracts, such as He2, with high concentrations of ERGO are potent nootropics capable of enhancing these two vital functions, which can potentially prolong the number of years we live disease free and boost overall longevity. With the current evidence sparking some excitement in the health and wellness community, it’ll be interesting to see what researchers find in future clinical trials.