Research links exercise to reduced inflammation and slower aging

Fresh insight into how regular movement protects the body from aging comes from a long-running study published in Cell. The work, led by scientists at the Chinese Academy of Sciences and Xuanwu Hospital Capital Medical University, reveals that the body does not simply react to exercise at the level of muscles or the heart. Instead, it relies on a whole network of genes, proteins, and chemical signals that shift over weeks, not minutes.

The research also highlights an unexpected player in this process. A small molecule called betaine, which builds up in the kidney during steady training, seems to help carry the long-term benefits of physical activity across the body.

This project followed 13 healthy men for six years, giving researchers an unusual look at how the body responds to both a sudden workout and a repeated training routine. Multiomics tools allowed the team to track changes in gene expression, protein levels, metabolic activity, and even gut microbes. That wide lens helped them separate the brief shock that follows a hard run from the deeper adjustments that come with training over time.

The participants were assessed at rest, after a single 5 Kilometer run, and after almost a month of running daily. What was surprising was the contrast between the two types of activity.

One strenuous acute bout of exercise induced inflammation, disturbed the metabolic signals in the body, and momentarily shifted the cells into what the scientists described as “metabolic chaos.” These responses subsided within hours, but, they provided some insight into how new exercise regimens can feel exhausting.

On the other hand, steady training provided a very different narrative. Over 25 days, the men developed a biological profile associated with resilience and slower aging. The team observed that the kidney was involved in some of these changes and discovered that the kidney increased the production of betaine through the enzyme CHDH.

As levels of betaine increased, inflammation decreased, cellular aging slowed, and energy expenditure improved. The gut seemed to get into the act, too, again in some beneficial way. They observed increased populations of gut bacteria that supply greater immune strength and antioxidant activity.

The researchers also observed improvements in T cells, the white blood cells that help protect the body against infection. Long-term exercise improved the stability of DNA integrity in these T cells and modified epigenetic characteristics associated with aging, including the gene regulator ETS1, decreasing to more youthful levels. These changes explained how continual exercise promotes a healthier immune system over time.

The findings offer clarification in addressing a question many “know” but rarely voice. When one exercises heavily, it is indeed stressful to the body. However, with months of training, the body has more strength and, generally, is calmer.

The investigation indicates that prolonged exercise activates pathways that promote recovery and adaptation. The temporary stress of a single exercise is regulated by IL-6 and corticosterone; however, repeated training activates the kidney-betaine-TBK1 pathway, which gradually returns the system to a healthier state.

Betaine is the centerpiece of their findings. In human blood and mouse tests, this molecule was able to link exercise to reductions in inflammation, cognitive performance, metabolic stability, and even mood regulation in aged animals by binding to and inhibiting TBK1, a protein that promotes chronic inflammation. When TBK1 is inhibited, the IRF3 and NF kappa B pathways are suppressed, resulting in reduced age-related inflammatory signals.

Betaine is well known as a nutrient in beets, spinach, and whole grains; it is also synthesized by the body. In this study, betaine emerged as a messenger molecule linking exercise to healthy aging. Supplementation with betaine in older mice found similar improvements as long-term exercise training. While it cannot replicate the multi-faceted benefits of exercise, it can be a substitute for limited individuals with exercise challenges.

Dr. Liu Guang Hui, a co-corresponding author, remarked on how "these findings provide a foundation for geroprotective treatments that can adjust how multiple organs interact." He goes on to suggest that taking betaine as a supplement could broaden the exercise benefits to those with barriers.

The findings provide avenues for new approaches to healthy aging. By elucidating how long-term physical activity improves immune function and slows cellular decline, while potentially replicating with betaine, the study lays the groundwork for therapeutic options that achieve similar effects.

Betaine may provide a safe and low-cost option for individuals unable to exercise regularly, while guiding future explorations of organ-to-organ communication.

This could lead to therapies that target kidney inflammatory control and youth-like behavior in organs.

Research findings are available online in the journal Cell.

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