One cause of aging is damage that affects the function of the critical macromolecules that make up cells: DNA, proteins, lipids and carbohydrates¹. Dysfunctional molecules can result from environmental factors such as reactive oxygen species ("free radicals") or simply from the spontaneous chemical reactions that occur in every cell.

Some kinds of molecular damage can be detected and repaired by cellular enzymes. We are studying PCM, an enzyme that repairs proteins impaired by a specific chemical change, the conversion of normal amino acids to isoaspartate². PCM is almost universal in living things and can restore the activity of damaged enzymes in vitro. Researchers working on bacteria, plants, nematodes, fruit flies and mice have shown that PCM is important for aging and/or long-term survival in each of these organisms.

There is a lot that we don't know about how PCM works in a living cell. For example, Are there certain crucial proteins that must be repaired, or is this a "maintenance" enzyme for all proteins? Exactly where and when is PCM important? How does it interact with other protein repair and maintenance systems? How does isoaspartate affect protein function in the cell? We hope to answer some of these questions using the bacterium Escherichia coli. Specifically, we are looking at the effects of mutations that inactivate the pcm gene and leave the cells unable to carry out this form of protein repair.

To learn more about PCM and protein repair, please click here, or follow the links at left; to see what's new in the lab, click here

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¹The National Institute on Aging publication "In Search of the Secrets of Aging" provides a good overview of aging research for the general public. Among many recent scientific reviews is Finch, C. E., and G. Ruvkun. 2001. The Genetics of Aging. Ann. Rev. Genomics Hum. Genet. 2:435-462.

²For a recent review, see Clarke, S. 2003. Aging as war between chemical and biochemical processes: protein methylation and the recognition of age-damaged proteins for repair. Ageing Res. Rev. 2:263-285.