L-Arginine Exerts Excellent Anti-Stress Effects on Stress-Induced Shortened Lifespan, Cognitive Decline and Depression

Abstract

The anti-stress potential of dietary L-arginine (Arg) was assessed in psychosocially stress-loaded senescence-accelerated (SAMP10) mice. Although this strain of mouse is sensitive to stress, daily administration of Arg at 3 mg/kg significantly suppressed aging-related cognitive decline and behavioral depression at nine months of age and counteracted stress-induced shortened lifespan. To investigate the mechanism of the anti-stress effect of Arg in the brain, early changes in oxidative damage and gene expression levels were measured using SAMP10 mice that were stress-loaded for three days. Increased lipid peroxidation in the brains of stressed mice was significantly lowered by Arg intake. Several genes associated with oxidative stress response and neuronal excitotoxic cell death, including Nr4a1, Arc, and Cyr61, remarkably increased in response to psychosocial stress; however, their expression was significantly suppressed in mice that ingested Arg even under stress conditions. In contrast, the genes that maintain mitochondrial functions and neuronal survival, including Hba-a2 and Hbb-b2, were significantly increased in mice that ingested Arg. These results indicate that Arg reduces oxidative damage and enhances mitochondrial functions in the brain. We suggest that the daily intake of Arg plays important roles in reducing stress-induced brain damage and slowing aging.

Green Tea Suppresses Brain Aging

“…As regards the actions of theanine in humans, a relaxing effect [ 26 ], stress reduction [ 24 , 25 ], and a reduction in depression and schizophrenia [ 72 ] have been reported. On the other hand, little attention has been paid to the functionality of arginine in green tea, but it has been revealed to have an excellent stress-reducing effect, similar to that of theanine [ 27 , 28 ]. Here, we focus on the suppression of brain aging via the stress-reducing effects of theanine and arginine and introduce a partially elucidated mechanism.…”

“…The median survival time (MST) was significantly longer in SAMP10 mice ingesting arginine (3 mg/kg) under stress-loading conditions (16.6 months) than in mice receiving no arginine (10.5 months) [ 28 ]. The dose of arginine was based on data regarding the suppression of adrenal hypertrophy, which was observed to occur at approximately half the dose of theanine.…”

“…However, under stress-loading conditions, it has been found that learning ability declines as early as 8 months of age, indicating that stress promotes a decline in brain function [ 77 ]. On the other hand, no reduction in brain function has been observed in stress-loaded mice ingesting theanine or arginine [ 28 , 77 ]. Since the brain consumes a large amount of oxygen, it is susceptible to oxidative damage due to the production of many reactive oxygen species (ROS) during the metabolic process [ 78 ].…”

“…Next, to investigate the mechanism of the anti-stress effect of arginine, early changes in gene expression levels were measured in SAMP10 mice on day three of stress loading [ 28 ]. The genes that maintain mitochondrial functions and neuronal survival, including hemoglobin alpha, adult chain 2 ( Hba-a2 ) and hemoglobin beta, adult minor chain ( Hbb-b2 ), were significantly increased in mice that ingested arginine.…”

“…Theanine, the most abundant free amino acid in green tea, has been found to relieve stress and have a relaxing effect [ 22 , 23 , 24 , 25 , 26 ]. In addition, arginine, which is the second most abundant free amino acid in Japanese green tea, has an anti-stress effect similar to theanine [ 27 , 28 ]. However, since the stress-reducing effects of theanine and arginine are counteracted by EGCG and caffeine, the composition ratio of these components is important for the anti-stress effect of green tea [ 27 , 29 ].…”