These proteins also influence the progression of some neurodegenerative diseases.
Researchers at the University of California, San Francisco (UCSF) say that they have overturned the belief that insoluble protein clumps are unique to degenerative disease and created by proteins specific to those diseases. In their study conducted in C. elegans they found that widespread protein insolubility and aggregation is an inherent part of aging, and it may influence both lifespan and neurodegenerative diseases. Reporting in PLoS Biology, the team also found that gene manipulations that extend the lifespan of C. elegans prevented the formation of these insoluble aggregates.
In neurodegenerative diseases such as Alzheimer and Huntington, clumps of proteins known as aggregates appear in patients’ brains as the degeneration progresses. The clumps contain proteins unique to the specific disease as well as many others that are common in healthy individuals. These common proteins were thought to be accidental inclusions in the aggregates.
In their study the UCSF research group sought to understand whether normal proteins form insoluble clumps when healthy individuals age. They say that they may not be innocent bystanders at all, but instead their presence may influence the course of neurodegenerative disease.
“If you take people with Alzheimer’s and look at their aggregates, there are many other proteins in the clump that no one has ever paid much attention to,” according to UCSF professor Cynthia Kenyon, Ph.D., director of the Larry L. Hillblom Center for the Biology of Aging at UCSF and senior author of the paper. “It turns out that about half of these proteins are aggregating proteins that become insoluble as a normal part of aging.”
The researchers identified roughly 700 proteins in a normal C. elegans worm that become insoluble with age. In the presence of proteins specific to Huntington disease, these aggregators actually sped up the course of the disease.
These insoluble proteins are highly over-represented in the aggregates found in human neurodegeneration, according to the scientists. Yet even in the healthy aging worms, these proteins had a propensity for clumping and forming hard, rock-like structures. The researchers found that many of the proteins that become insoluble during normal aging are proteins already known to accelerate the aging process and to influence the aggregation of the major disease proteins.
Their aggregation was significantly delayed or even halted by reducing insulin and IGF-1 hormone activity, whose reduction is known to extend animal lifespan and to delay the progression of Huntington and Alzheimer disease in animal models, they add.