Molecular Chaperones Decline with Age
Chaperone proteins work to ensure correct protein folding and function in cells. The more chaperone activity taking place, the less damage in the form of dysfunctional protein machinery at any given time. Artificially boosting forms of chaperone activity is a potential form of treatment for some of the causes and consequences of age-related degeneration, as it could turn back the clock on rising levels of misfolded and otherwise damaged proteins.
Aging is the most significant and universal risk factor for developing neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's, Parkinson's and Huntington's diseases. This risk increases disproportionately with age, but no one really knows why. Now a team of [scientists] has uncovered some clues. The researchers are the first to find that the quality of protective genes called molecular chaperones declines dramatically in the brains of older humans, both healthy and not, and that the decline is accelerated even more in humans with neurodegenerative disease.Molecular chaperones are a special set of highly conserved genes that watch over cells, keeping them and the entire organism healthy by preventing protein damage. The researchers specifically found the decline in 100 genes, approximately one-third of all human molecular chaperone genes. Then, with additional studies, they winnowed that number down to 28 human genes specifically involved in age-associated neurodegeneration. These critical genes provide a basis for a biomarker, an early indicator of disease and a target for new therapeutics.
"Imagine if we had biomarkers that tell doctors how you are doing in terms of aging, warning of any problems long before neurological deficits appear. This would be a remarkable tool, especially considering the increases in life expectancy in many parts of the world. Let's say a person is age 50, but we see his molecular chaperones have declined and aren't repairing proteins and cellular damage. The chaperones are acting more like age 85 or 90. That's a sign that medical intervention could help. Molecular chaperones really are the barrier we have between disease and no disease. If this critical system declines, it leads to misfolded and damaged proteins, and eventually tissues become dysfunctional and die. If we can keep the chaperones healthy, we should be able to keep the person healthy. The next step is to understand the basis for the decline of these specific chaperones and to develop treatments that prevent their decline. The goal is not to make people live forever but rather to match health span more closely with life span - to improve the quality of life being lived."