Biocurious

/ a biophysics blog

Hot off the Press: Mitochondrial DNA mutations and aging in mice

Posted 15 July 2005 by PhilipJ under

As reported in today’s issue of Science, mice expressing mutated mitochondrial DNA polymerases (POLG) deficient in a proofreading mechanism (that is, no longer having the ability to “spellcheck” ongoing transcription) displayed accelerated aging. The mutation to POLG was minor, with a simple substitution of two bases in the exonuclease domain, but this region of the protein is so highly conserved that even a small a substitution results in a misfolding of the active site (proofreader).

With POLG unable to fix errors in transcription, the mice accumulated mutations in their mitochondrial DNA (mtDNA) faster than wild type mice. They also exhibited signs of accelerated aging, such as losing hair, greying, the loss of muscle mass, and an increased level of apoptotic markers. Furthermore, their average lifespan was roughly half that of wild type mice!

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