PARP1 Activation Associated with Overtraining Syndrome in Mice and Humans

Excessive physical exercise without sufficient rest can harm the body, sometimes leading to overtraining syndrome. This condition is marked by reduced performance, chronic fatigue, muscle pain, increased injuries, changes in appetite, and alterations in the immune system and metabolism. A recent study published in Molecular Metabolism investigated the underlying causes of this syndrome.

Researchers from the State University of Campinas found that mice subjected to excessive exercise displayed symptoms such as performance loss, fatigue, and behavioral changes. These effects were linked to the overexpression of the PARP1 protein in skeletal muscles. According to Barbara Crisol, first author of the study, “The protein is activated when there’s some stress in the body, preventing cell death, and has been well described as increased in skeletal muscle in conditions of obesity and muscular dystrophies. We confirmed that its hyperactivation is related to muscle damage caused by excessive exercise.”

Currently, the only way to address overtraining syndrome is by reducing or stopping training, sometimes for weeks or months. The researchers also found that mice treated with a drug that inhibits PARP1 did not develop overtraining symptoms. However, senior author Eduardo Ropelle cautioned, “this isn’t a drug that can be used for this purpose, as it has several side effects, including suppressing the immune system.”

In a related human study in Sweden, healthy volunteers underwent high-intensity interval training with limited recovery time. Muscle biopsies revealed decreased glucose tolerance, reduced mitochondrial function, and lower physical performance. Crisol’s analysis showed increased muscle paralysis linked to PARP1 activity. The researchers are now seeking natural compounds that could inhibit PARP1 safely, which may help prevent or treat overtraining and other muscle-related conditions.