Science: Exercise makes the brain younger! UCSF scientists have found for the first time that exercise allows the liver to release an enzyme that promotes nerve regeneration and improves cognitive scientific discoveries.

There are so many benefits of exercise.to say that the most exciting function of exercise is the influence on the brain.many studies have shown that exercise can delay or even reverse the effect of aging on the brain, and improve cognitive decline and neurodegenerative diseases [1-3].however, the mechanism behind this is still unknown.today, a research team led by Dr. Saul a. Villeda of the University of California, San Francisco, published an important research result in the top journal Science [4], which gives us a glimpse of the reasons why exercise is beneficial to brain health.for the first time, they found that after exercise, the liver of mice would synthesize a large amount of enzyme called gpld1, which could promote the regeneration of hippocampal neurons and improve the cognitive ability of aging mice.in addition, they also found an increase in gpld1 levels in the blood of healthy, active elderly people.more importantly, based on this study, Villeda's team also found that as long as the ability of mice's liver to produce gpld1 is increased, even if the mice don't exercise, they can gain the benefits brought by exercise to the brain."if there is a drug that produces the same brain benefits as exercise, everyone should want to take it," Villeda said [5], "now our research shows that at least one day some of these benefits may come in the form of pills."} UCSF scientists have made exaggerated illustrations. Although Villeda's research results have partially uncovered the mystery that exercise is beneficial to the brain, Villeda's original purpose is not to solve the mystery, but to help people who can't exercise.because there are so many benefits of exercise, especially for the brain, many elderly people or people who are unable to move due to diseases can not enjoy the benefits of exercise.Villeda decided to "transplant" the benefits of exercise to people who were not able to exercise.Villeda noted that in many animal studies, exercise can reverse the age-related neurogenesis and cognitive decline in the hippocampus [6-8].similarly, transferring blood from young mice to old mice can also improve tissue cell regeneration and cognitive ability of mice [9-12].these two types of studies lead Villeda to think whether the benefits of exercise on the brain are achieved through blood? So there was this study.} the robust Dr. Saul a. Villeda is not suitable for this pose after confirming that exercise can indeed promote neurogenesis and improve the hippocampus dependent learning and memory ability of aged mice.Villeda wanted to see if the brain benefits of exercise could be "transferred" to inactive mice through plasma. so the researchers collected blood from exercise-induced and non exercise aged mice and separated the bleeding plasma. the plasma was then injected into the sedentary old mice in eight times over a three week period. in the following time, the cognitive ability of mice was studied first, and then the neurogenesis was studied. } research flow chart from the results, the learning and memory abilities of old mice receiving exercise mice plasma were improved, and the corresponding regeneration ability of hippocampal neurons in elderly mice was also increased. Although neural stem cells did not increase, the number of new neurons did increase. in order to understand whether the blood of young mice has the same effect, the researchers repeated the experiment with young mice, and found that the plasma of young exercise mice can also promote the increase of neurons in the hippocampus of old mice. that means that the benefits of exercise on the brain are reflected in both young and old mice. } the first line is neural stem cells, the second and third lines are regenerated new nerve cells, which confirm that exercise can improve brain health through plasma. Although Villeda and his colleagues are excited, this method is too difficult to apply in reality. the best way is to find specific single effector molecules. as a result, Villeda's team analyzed the plasma proteins of old or young mice in exercise or rest. they found that the abundance of 30 factors increased in old mice after exercise, 63% of which were mainly expressed in the liver; 33 factors increased in young mice after exercise, with 67% mainly expressed in the liver. the abundance of 12 species in the plasma of aged mice and young mice were increased, and the largest increase was gpld1 and PON1. } high abundance factor analysis Villeda and his colleagues chose to focus on GPI degrading enzyme gpld1 because no previous studies have shown that gpld1 is related to aging, neurogenesis or cognition. after the discovery of gpld1, the first thing the researchers did was to see whether there was a real correlation between plasma gpld1 levels and cognitive ability. they compared the plasma gpld1 levels of exercise and sedentary old mice and found that there was a significant correlation between the increase of gpld1 concentration and the improvement of cognitive ability. is there any relationship between exercise and gpld1 level in the elderly? One analysis, it is true that the level of gpld1 in the plasma of the elderly who love exercise is significantly higher than that of the sedentary elderly. this indicates that exercise can induce the increase of plasma gpld1 concentration in both old mice and elderly people. this makes it possible to realize the benefits of "transplanting" exercise on the brain. } human data analysis since gpld1 improves the cognitive ability of aged mice, where does gpld1 come from? Villeda and his colleagues analyzed the expression levels of gpld1 mRNA in more than ten tissues and organs of mice, and the results showed that the level of gpld1 mRNA in liver was the highest, which was also consistent with the previous research results [13]. this indicates that gpld1 in plasma after exercise is mainly synthesized by liver. subsequently, the researchers analyzed the relationship between gpld1 expression in the liver and aging and exercise. excluding the exercise variables, the expression level of gpld1 in liver did not change with the aging of mice, even if the plasma of exercise mice was infused. however, exercise changed the level of gpld1 expression in the liver, which was increased in exercise mice compared with static mice. in addition, gpld1 in muscle and hippocampus did not change under any condition. } analysis of gpld1 expression in different tissues and organs, and comparison of gpld1 levels in liver after resting and exercise, in order to detect the effect of gpld1 on the brain of aged mice. the researchers selected a vector to target hepatocytes, then linked up the gene encoding gpld1 and the gene encoding green fluorescent protein, respectively, and injected them into old mice. after the injection of the carrier with gpld1, the plasma gpld1 concentration increased and the hippocampal neurons increased in the inactive elderly mice. The cognitive test results showed that the cognitive ability of the elderly mice was also improved. in fact, the researchers also tested PON1 screened out with gpld1 at this step. Unfortunately, increasing the plasma level of PON1 did not improve the cognitive function of aged mice under the same conditions. the next question is how exercise-induced gpld1 improves brain function. preliminary results show that the signal level of gpld1 in the brain is several orders of magnitude lower than that in the plasma, indicating that gpld1 does not seem to enter the brain easily. then gpld1 can only regulate brain health by affecting its substrate. if so, the signal cascade formed by gpld1 cleaving its substrate GPI is a necessary condition for gpl1 to affect the hippocampus of aged mice. } the mechanism of exercise improving the brain in general, Villeda and his colleagues found that the beneficial effects of exercise on the elderly brain can be transferred to the non exercise elderly brain through blood components. and one of the key factors is the synthesis and secretion of gpld1 by hepatocytes. Gpld1 triggers the downstream signal cascade reaction by cracking the substrate, which promotes the regeneration of hippocampal neurons and the improvement of cognition. "the liver responds to the body's movement through gpld1 protein and makes the aging brain younger," Villeda said. "this is an extraordinary example of how the liver communicates with the brain, as far as we know, no one knew it existed before us. It is understood that the laboratories of Villeda are fully studying gpld1 to find out how gpld1 interacts with other biochemical signal systems and ultimately plays a beneficial role in the brain. they hope that through their in-depth research, they can determine specific therapeutic targets and one day make people who can't exercise benefit from the benefits of exercise on the brain. although ASCO in 2020 is over, its impact on cancer treatment in the next few years is just beginning. in order to help you quickly grasp the key points of this year's ASCO and effectively obtain a panoramic understanding of the frontier progress, we have also made full efforts to create the "asco2020 trend interpretation". it comprehensively combs the 9 major cancer species and the key academic research in 300 oral reports, so as to give you a comprehensive overview of the progress of ASCO in 90 minutes.