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Chaperone overload is a possible contributor to 'civilization diseases'
1Dept of Medical Chemistry, Semmelweis University, PO Box 260, H-1444 Budapest, Hungary. csermely@puskin.sote.hu
Trends in Genetics : TIG
|November 24, 2001
Summary
Modern medicine may increase harmful mutations by reducing the natural selection of silent mutations. Increased misfolded proteins in aging individuals exacerbate this, potentially contributing to complex diseases.
Area of Science:
- Genetics
- Molecular Biology
- Evolutionary Medicine
Background:
- Molecular chaperones normally buffer the effects of deleterious mutations, preventing their accumulation.
- Modern medical practices may have inadvertently reduced natural selection against these mutations.
- Aging is associated with increased misfolded proteins, potentially interfering with chaperone function.
Purpose of the Study:
- To propose the 'chaperone overload' hypothesis.
- To explain the rise of phenotypically silent mutations in the human genome.
- To link chaperone function, aging, and the manifestation of multigene diseases.
Main Methods:
- Theoretical modeling of chaperone buffering capacity.
- Review of existing literature on molecular chaperones and aging.
- Analysis of the evolutionary impact of medical interventions.
Main Results:
- Modern medicine may have decreased the removal of mutations by natural selection.
- Aging-related increase in misfolded proteins can overwhelm chaperone systems.
- This "chaperone overload" may expose previously silent mutations, contributing to disease.
Conclusions:
- Enhanced chaperone capacity is crucial for aging individuals.
- Understanding chaperone buffering is key to addressing silent mutations.
- This hypothesis may guide strategies for identifying and repairing mutations.