McMaster University researchers have discovered a previously unknown cell-protecting function of a protein called MANF, which could lead to new treatments for age-related diseases and promote healthier aging. The team found that MANF plays a role in maintaining cellular homeostasis, the process that keeps cells efficient and functioning properly. As we age, our cells’ ability to maintain homeostasis declines, leading to protein aggregation that has been linked to diseases like Alzheimer’s and Parkinson’s. MANF protects against increased cellular stress and helps break down accumulated proteins, keeping cells healthy and free of clutter.
The team’s findings, published in the journal Proceedings of the National Academy of Sciences, were based on studies of microscopic worms known as C. elegans. By manipulating the levels of MANF in these worms, the researchers were able to observe its role in the cell’s disposal process. MANF was found to be present in lysosomes, structures associated with lifespan and protein aggregation, within various tissues of the worms. Increasing MANF levels activated a natural clean-up system within cells, promoting better cellular functioning and longevity.
While the research focused on worms, the researchers believe that the processes they uncovered are universal and applicable to all animals, including humans. By understanding how MANF works and identifying its interactions with other players in the cell, researchers hope to develop new treatments for diseases affecting the brain and other parts of the body. Targeting cellular processes to clear out toxic protein clumps and maintain cellular health could lead to developments in treating age-related diseases and promoting longer, healthier lives.
Biology professor Bhagwati Gupta, who supervised the research, explained how cells respond to stress caused by protein aggregation. When proteins clump together, the endoplasmic reticulum, where proteins are made and released, receives a signal to stop producing these proteins. If the problem can’t be corrected, the cell ultimately dies, leading to degeneration of neurons and the development of neurodegenerative diseases. Understanding how MANF protects cells against stress and promotes efficient cellular processes could lead to the development of new therapies for age-related diseases.
Researcher Shane Taylor, now a post-doctoral fellow at the University of British Columbia, conducted his PhD work on the project at McMaster. Taylor and the team found that MANF helps to break down accumulated proteins within cells and activate a natural clean-up system, ultimately maintaining cellular health and function. By targeting MANF’s function, researchers hope to develop treatments for age-related diseases by making cellular processes more efficient. The central idea of aging research is to develop ways to improve cellular processes and promote longer, healthier lives, and proteins like MANF could play a key role in achieving this goal.
