Vigorous exercise, fasting, hormones improve elimination of toxic, misfolded, unnecessary proteins in mouse, human cells

The body's ability to adapt to changing conditions and shifting physiologic demands is essential to survival. To do so, each cell must be able to dispose of damaged or unnecessary proteins a quality-control mechanism critical for cellular performance and for the health of the entire organism. Now, a study from Harvard Medical School shows that intense exercise, fasting and an array of hormones can activate cells' built-in protein disposal system and enhance their ability to purge defective, toxic or unneeded proteins. The findings, published Feb. 19 in PNAS, reveal a previously unknown mechanism used by the body to rapidly turn on the molecular machinery responsible for junk-protein removal, allowing cells to adapt their protein content to meet new demands. This mechanism, the study shows, is triggered by fluctuations in hormone levels, which signal changes in physiologic 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 in the Blavatnik Institute at Harvard Medical School.