Exercise contributes to health and anti-aging. But what exactly makes exercise have such miraculous effects? Our research team spent 6 years systematically analyzing the molecular cellular dynamic response spectrum of the human body to acute single exercise and long-term regular exercise for the first time, revealing that the kidney is a key response organ for exercise effects - its endogenous metabolite betaine acts as a core molecular messenger for aging delay, synergistically inhibiting the natural immune hub kinase TBK1, suppressing inflammation, and alleviating multi organ aging process. This research was jointly completed by Liu Guanghui and Qu Jing, researchers of the Institute of Zoology, Chinese Academy of Sciences, Zhang Weiqi, researchers of the National Center for Biological Information, Song Mozhi, researchers of the Institute of Zoology, Chinese Academy of Sciences, and Wang Si, researchers of Xuanwu Hospital, Capital Medical University. Recently, the relevant paper was published in the international academic journal Cell. In previous studies, the research team has achieved many results in this area. For example, the system characterized the cellular and molecular response characteristics of 14 organ tissues in young and old mice to long-term aerobic exercise, analyzed the dynamic network of inter organ collaborative response at the spatiotemporal scale, and accurately elucidated the integrated mechanism of exercise in delaying aging by reshaping the rhythm factor regulatory network, activating angiogenesis signals, inhibiting chronic inflammation in multiple organs, and other core pathways. This provides a new perspective for understanding the systemic anti-aging effect of exercise. But do the conclusions of mouse studies also apply to humans? In this study, the team recruited 13 healthy male volunteers and conducted a rigorously designed self controlled trial. The experiment is divided into three stages: the first stage is a 45 day "resting" baseline period, in which strict standardized procedures are used to control for exercise variables and confounding factors such as diet/sleep; The second stage is the acute exercise phase of running for 40 minutes and 5 kilometers at once; The third stage is a 25 day long-term regular exercise period, gradually transitioning from once every other day to a daily 5-kilometer run. Researchers constructed a multimodal data coupling analysis framework by collecting blood and fecal samples from volunteers at different time stages, combined with health examination data, and using multi omics analysis methods. With the help of this framework, researchers have for the first time deconstructed the complex systems biology problem of adaptive response to exercise into a quantifiable multi omics dynamic network, systematically analyzing the physiological adaptation performance and mechanisms after a single acute exercise and long-term regular exercise. So, how does exercise delay aging? Scientists have made three important discoveries. Firstly, the effects of acute and long-term exercise are different. Acute exercise triggers a "survival stress type" metabolic storm and oxidative damage, while long-term exercise drives a health oriented metabolic immune homeostasis remodeling and establishes a multidimensional adaptive system supported by metabolic reprogramming, immune rejuvenation, epigenetic stability maintenance, and antioxidant capacity enhancement. At the same time, long-term exercise synchronously reshapes the structure of intestinal microbiota, inhibits the abundance of pathogenic symbiotic bacteria, and synergistically regulates the body's energy metabolism. Secondly, long-term exercise can reshape the youthful state of T lymphocytes. By enhancing the genomic and epigenetic stability of peripheral immune cells, activating the NRF2 pathway to suppress the expression of inflammatory factors and immunosuppressive receptors, and promoting T cell survival, proliferation, and differentiation, T cell aging can be delayed. Thirdly, long-term exercise can induce endogenous synthesis of betaine in the kidneys. In mouse experiments, it was found that betaine can prolong the healthy lifespan of mice and significantly improve five functional indicators: metabolic capacity, renal function, exercise coordination, depression like behavior, and cognitive ability. The integrated analysis of histopathology and single-cell transcriptome further confirms that betaine has the effect of delaying multi organ aging, especially in the kidneys and skeletal muscles. At the same time, scientists have also deciphered the mystery of betaine delaying aging - it can directly act on the natural immune kinase TBK1, effectively reducing immune cell infiltration and inhibiting the release of pro-inflammatory cytokines. This study has opened up a new paradigm for the development of "endogenous metabolite mediated exercise benefits", transforming complex physiological effects into quantifiable and actionable chemical language, and paving the way for aging interventions based on metabolic reprogramming. At the same time, it also has great prospects in clinical translation - researchers are accelerating the pharmacokinetic study of betaine in elderly chronic disease populations, building a quantitative correlation bridge between fluid levels and aging phenotypes; Through multi center clinical trials, verify the universality of the intervention and integrate biomarkers such as TBK1 phosphorylation to construct a precise evaluation system; In addition, exploring the synergistic drug strategy of betaine and developing highly selective derivatives to enhance anti-inflammatory and anti-aging effects. Although there are still some key scientific issues that need to be addressed, these findings have deepened our understanding of the health benefits of exercise and provided important scientific basis for advancing research on healthy aging. Science has proven the benefits of long-term exercise, what are you waiting for? Get moving! (New Society)