Premature Aging Caused by Low Telomerase Levels


Telomerase is an enzyme catalyzing critical steps in the replication of the exceptional chromosome tip structures, the telomeres. Telomeres require a replication mechanism distinct from that of the rest the chromosome, being comprised of multiple linear copies of a short DNA sequence. Telomeres progressively shorten over a life span, eventually limiting chromosome and cell replication. This is though to be one of the several defenses against tumors and cancer. In the June issue of Molecular and Cellular Biology, an ONRL team describes a new protein component of the telomerase complex. The ORNL team with collaborators at the University of Toronto explored effects of exceptionally low levels of telomerase, which was genetically engineered into the mouse. In the forthcoming April issue of Proceedings of the National Academy of Sciences, they report that low telomerase mice suffer premature aging effects, and so mimic a known human inherited disorder that causes premature aging. Thus a physiological balancing becomes evident. Too much telomerase activity in the adult may increase the risk of cancer, while too little promotes too rapid aging. This insight is one of many achieved by the ORNL researchers over the years, using the mouse as a model for inherited genetic diseases.