A new study has shown that vigorous exercise and fasting improve the ability of human and mouse cells to remove defective, toxic, or unnecessary proteins — responsible for some diseases in the body.


The researchers from the Blavatnik Institute at Harvard Medical School (HMS) discovered that intense exercise, fasting, coupled with the help of hormones can activate cells’ built-in protein-disposal systems and enhance their ability to purge defective, toxic, or unneeded proteins.

The research, which was published in PNAS on February 19, showed a previously unknown mechanism that activates the cells’ protein-disposal machinery, allowing them to adapt their protein content to shifting demands and new conditions.

“Our findings show that the body has a built-in mechanism for cranking up the molecular machinery responsible for waste-protein removal that is so critical for the cells’ ability to adapt to new conditions,” said Alfred Goldberg, senior author on the study and professor of cell biology at the Blavatnik Institute.


During the experiments, the researchers examined the effects of exercise on cells obtained from the thigh muscles of four people before and after vigorous biking.

The exercise allowed the proteasomes of these cells to display dramatically more molecular marks of enhanced protein degradation, including greater levels of cAMP, the chemical trigger that initiates the cascade that leads to protein degradation inside cells.

The same changes were observed in the muscles of anesthetized rats whose hind legs were stimulated to contract repeatedly.


Bear in mind that proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis — a chemical reaction that breaks peptide bonds.

Fasting — even for a short while — produced a similar effect on the cells’ protein-breakdown machinery by increasing proteasome activity in the muscle and liver cells of mice deprived of food for 12 hours — the equivalent of an overnight fast.

The findings showed that the rate of protein degradation can rise and fall swiftly in a variety of tissues in response to shifting conditions and that such changes are mediated by fluctuations in hormone levels.

“We believe our findings set the stage for the development of therapies that harness the cells’ natural ability to dispose of proteins and thus enhance the removal of toxic proteins that cause disease,” said Jordan VerPlank, study lead investigator and postdoctoral research fellow in cell biology in the Blavatnik Institute at Harvard Medical School.


The researchers, while admitting the many salutary effects of exercise, also suggested, in the new findings, the possibility that exercise and fasting could help reduce the risk of developing conditions associated with the accumulation of misfolded proteins, such as Alzheimer’s and Parkinson’s.

“That possibility, however, remains to be explored in subsequent research,” the team noted.

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