Attack of the Anti-Killer Tomatoes: NMN and a Tomato-Derived Antioxidant Support Healthy Cognitive Function in Aging Rats

Like an overripened tomato, our brains go to mush with age, often leading to the gradual loss of learning and memory abilities and cognitive impairment. New findings revealed that the combination of nicotinamide mononucleotide (NMN) and lycopene, a proven antioxidant found in tomatoes, exerts a potent effect in not only supporting cognitive function in aging rats but also decreasing oxidative stress in both aging rats and cultured senescent rat brain cells. Based on these results, the combination of NMN and lycopene may be an attractive proposition for developing a novel product that supports healthy brain aging and cognitive function. 

Can antioxidants and NAD+ fight off aging?

Brain aging is affected by a slew of genetic and environmental factors, which often manifest through alterations in diverse metabolic processes and cell signaling pathways. One such process that often goes awry pertains to free radicals, unstable compounds that can damage cells by causing oxidative stress. The accumulation of free radicals typically causes cellular functional impairment and aging. That’s why purported antioxidants like berberine, resveratrol, and curcumin are drawing growing attention in the search for compounds that support healthy aging. In recent years, increasing studies have provided evidence that a compound highly prevalent in tomatoes called lycopene confers a potent oxygen-free radical-scavenging ability, which could protect various types of cells and organs from oxidative damage. 

It is widely accepted that cellular nicotinamide adenine dinucleotide (NAD+) is essential for normal cellular replication and function, the regulation of metabolism, and the normal activation of anti-aging pathways. As reported, the availability of cellular NAD+ is decreased with advanced age; hence, restoring cellular NAD+ is also a potential strategy for promoting healthy aging. NMN is an intermediate of NAD+, which has been reported to potently mitigate age-associated physiological decline in rodents. Also, previous studies have reported that NMN restored levels of NAD+ to reduce oxidative damage in the brains of aged rodents.

NMN and lycopene support healthy cognitive function in aging rats

In a study published in the journal Gene, the Chinese researchers explored the anti-aging effect of combining NMN and lycopene in rats. To model aging, Xuxin Liu and colleagues treated rats and cultured rat brain cells with a compound called D-gal. Multiple studies have reported that chronic exposure to D-gal could induce premature senescence – an aging-related state where cells no longer grow or replicate. Using the Morris water maze, a test for visual-spatial memory in which mice learn to use visual cues to find a hidden platform in a murky pool, the Chinese researchers showed that the cognitive defect caused by D-gal was improved by treatment with either NMN or lycopene. When used in combination, NMN and lycopene treatment led to a more significant improvement in supporting cognitive function.

Reducing senescence by inhibiting oxidative stress

Continuously injecting high doses of D-gal has been shown to cause oxidative stress, thereby inducing aging in cells and tissues. In agreement with previous studies, this study observed a remarkable decline in the levels of major antioxidant enzymes and a significant increase of malondialdehyde (MDA) – an indicator of membrane damage caused by oxidative stress – in both aging rat brains and senescent rat brain cells induced by D-gal.

In addition, D-gal also leads to metabolic abnormalities, increased inflammatory response, tissue damage, and, finally, liver aging. In this study, D-gal stimulation also caused an imbalance in the antioxidant system in the liver. NMN and lycopene mitigated the oxidative stress of rat brains and livers as well as cultured senescent rat brain cells by elevating the levels of antioxidant enzymes and reducing MDA levels. NMN and lycopene effectively reduced senescence, as shown by various tests, including those for the activity of genes and proteins that indicate senescence.

Is there an NMN-lycopene combination product on the horizon?

Based on these data, Xuxin Liu and colleagues proposed that the combination of NMN and lycopene could protect cognitive impairments associated with aging by reducing oxidative damage by restoring the antioxidant defense system. Xuxin Liu and colleagues conclude, “Collectively, our results showed that the combination of NMN and lycopene could induce a more potent effect on improving cognitive deficits and reducing cellular senescence partly through the potentiation of the anti-oxidative route.”

References:

Liu X, Dilxat T, Shi Q, Qiu T, Lin J. Gene. 2022;822:146348.