Possible exercise mimetic: Betaine mediates positive effects of exercise

Physical exercise leads to different physiological adaptations depending on its duration and frequency. Acute physical exercise triggers immediate metabolic and immune responses to the physiological challenge, while regular physical training induces profound optimizations of various systems, including immune function, stem cell vitality, tissue regeneration capacity, and neuroplasticity, with improvements in cognitive performance. Chinese researchers led by Lingling Geng from the Aging Translational Medicine Center in Beijing have now described all of these effects in molecular detail in a publication in the journal Cell .

For the study, the researchers recruited 13 healthy male volunteers who initially completed a 45-day baseline phase (BL) with restricted exercise, followed by a single 5-km run (AE), and finally a 25-day long-term training (LE) protocol with daily 5-km runs. Blood (pre- and post-AE, as well as post-LE) and stool samples were analyzed. In addition, the researchers also conducted a comprehensive physical examination.

After a single running session, 24 of the 31 biochemical blood parameters and inflammatory markers examined changed significantly. Particularly striking was the 2.84-fold increase in free fatty acids (NEFA) and the decrease in total bile acids to 53 percent of the baseline value. Inflammatory factors also showed strong activation, particularly interleukin-6 (IL-6) and calgranulin C, the extracellular receptor for advanced glycogenase end product (EN-RAGE). Calgranulin C is a cytosolic protein found in granulocytes, monocytes, and keratinocytes.

Single-cell RNA sequencing also revealed a change in the relative abundance of about half of the peripheral blood cell types. In particular, the number of natural killer cells and CD8+ T cells increased while immature cells decreased. The researchers interpret this to indicate that the running session induced increased immune surveillance. This is evident, among other things, in the increased mobilization of certain immune cells into the blood . At the same time, stress hormones such as cortisone were released in increased amounts, and certain receptors on the immune cells (such as CXCR4) were activated. This suggests that the glucocorticoid-controlled metabolism was also activated.

The run resulted in increased formation of anaerobic glycolysis products (lactate, pyruvate), and increased levels of lipolysis markers (glycerol) and short-chain carnitine esters, which indicate increased β-oxidation. Amino acids were also almost completely consumed. Proteomic analyses also revealed that short-term physical activity is also associated with oxidative stress and tissue remodeling.