Haoran Zhang

1Department of oncology,Tianjin Nankai Hospital,Tianjin,China.

The question of how we live longer—and why only a minority of humans have good health and a long life—has confused people for millennia.Over the past few decades,we have learned that human lifespan is determined by both the genes and external influences,and that these factors act,by means of numerous genetic pathways,to regulate the cellular and systemic processes that ultimately cause aging and death.

Recently,a study by a team at Harvard Medical School,published in the journal Nature,reveals the first evidence of the link between the nervous system and aging.Professor Bruce Yankner and others have found that the overall neuronal excitation could determine the lifespan,which is more obvious in short-lived individuals than the long-lived.People with high levels of arousal live shorter lives,while people with long lives experience lower levels of neuro arousal [1].Besides,they also point out that the molecular mechanisms are associated with repressor element-1 silencing transcription factor (REST) gene expression level,which could reduce the nervous system excitability,adjust insulin and insulin-like growth factor 1 (IGF-1) signaling pathway and eventually promote longevity.

Interestingly,the theory that relaxation of nerves contributes to longevity had been recorded in ancient Chinese books before thousands of years.Writing in the classical ancient books of traditional Chinese medicine entitled Huangdi Neijing (Yellow Emperor's Canon of Internal Classic) (221 B.C.E.-220 C.E.),the Huang Di's teacher Qi Bo told him that people in prehistoric times could live more than 100 years,and they rarely showed signs of aging in old age [2].One of the reasons is that they know the way to maintain body heath.They have peaceful life and regular diet,never overworked or too tired because of the desire.Not only in traditional Chinese medicine but also in Buddhist theory,practitioners seek inner peace to keep themselves healthy.In modern society,there are also many examples of this,such as art therapy,Qigong(an ancient and widely practiced Chinese meditation exercise) therapy and martial arts practice,which are the pursuit of inner peace and spiritual relaxation,ultimately to maintain health and reduce disease.

How might this occur? First,previous studies have found that aging affects the nervous system,for example,Alzheimer's disease and other age-related neurodegenerative diseases [3,4].In contrast,some studies have found that neural signals can influence the rate of aging in living things [5].For example,the elimination of specific neurons in the nematode can change the lifespan of the nematode [6].The increased lifespan associated with reduced insulin/IGF signaling can be eliminated by restoring the function of specific neurons [7].But previous studies have looked only at the relationship between nematode nerves and lifespan,and no one has looked at whether the state of nervous system activity affects the aging process.

Aging is characterized by a progressive loss of physiological integrity,impairment of physiological function and eventual death.Aging causes a variety of diseases including cancer,diabetes,cardiovascular disease and neurodegenerative diseases.In recent years,the study of aging has made unprecedented progress,especially the discovery that the rate of aging is controlled by genetic pathways and biochemical processes preserved in the process of evolution.Numerous studies have identified many characteristics of aging:genomic instability,telomere wear,loss of protein stability,nutrient sensing disorders,mitochondrial dysfunction,cellular senescence and stem cell failure [8].By studying the molecular mechanisms of aging,we can look for drugs or methods to improve human health and prolong life in the future.

Studies have shown that the expression changes of brain genes in young and old people are very significant [9].The researchers collected three known brain transcriptome cohort studies:Religious Orders Study and Memory and Aging Project,CommonMind Consortium,and Gibbs [10-12].They then analyzed differences in gene expression between the long-lived group (older than 85 years) and the non-long-lived group (younger than 80 years) and found a surprising finding:people who died after age 85 had significantly lower expression of genes related to neural excitation than people who died before age 80.The results suggest that longevity may be related to lower neuron excitability.

So the question is whether signals from the nervous system can regulate the rate at which the whole body ages.Zullo and his colleagues began their study by studying the brain tissue of older adults who had no cognitive deficits before they died.The authors analyzed gene expression profiles in the frontal cortex and found an interesting correlation:in long-lived individuals,genes involved in neural excitation and the function of synaptic connections between neurons were downregulated,but genes needed to inhibit neurotransmission were not.

As early as 2014,Yankner's team noticed the role of REST in the brains of the elderly [13].The expression of many genes is regulated by this REST protein,which has a protective effect on the brain.Large traces of the REST gene were found in the long-lived population where the expression of the neuroexcitation-related genes was down-regulated.Moreover,the decreased expression of those genes did correlate positively with increased REST gene expression.To test this out more intuitively,they did it again in mice.They compared the level of neural activity in the brains of mice that had the REST gene knocked out with that of wild-type mice.The results are unequivocal:REST suppresses neural activity across the board and prevents the brain from getting too excited.In subsequent studies,the researchers found that the presence of a large number of REST proteins reduced neuronal excitability,which in turn activated the expression of the Forkhead box O 1 protein (daf-16 in nematode worms),a molecule downstream of the insulin/IGF signaling pathway,ultimately prolonging lifespan.We all know that the anti-aging effects of caloric restriction are also achieved by affecting the insulin/IGF signaling pathway.

For example,accumulating evidence couples neural overexcitation to Alzheimer’s disease [14].So REST and other molecules that control neural excitability are possible targets for interventions aimed at battling the decline and maladies of old age.What's more,the researchers found that their study was consistent with previous studies.For example,the anticonvulsants ethylsuccinate and valproic acid can extend the lifespan of nematodes [15].Activating REST or reducing neuronal excitability may be one way to slow down aging in humans.

In complementary and alternative medicine,there are many ways to calm your nerves and achieve inner peace.These ways of relaxing nerves have significant effects on delaying senility,treating mental illness and improving the quality of life of patients with chronic diseases.For example,during the process of music treatment,the participant transfers from depressed mood to deep relaxation and from the frightened state to the state of inspiration and creativity.Through arts therapy sessions and hospital tours,the music helps the depression patients deal with feelings of sadness,anxiety and anger[16].In addition,different schools of Qigong treatment also have a magical therapeutic effect.By relaxing and affecting nerves,Qigong,in addition to delaying aging,can significantly speed up the body's recovery process,and even grow new hair[17].Similar to Qigong,the traditional Chinese martial art of Tai Chi is a form of training that relaxes the nerves to slow the aging process[18-19].

In conclusion,whether through Qigong training,gene modification,or medication,it helps to slow down the overall changes in neural excitation and maintain the proper balance of neural network activity.In modern society,adequate rest and sleep are also the keys to preventing age-related neurological disorders and diseases.Evidence continues to suggest that inner peace may actually prolong human life.