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Study of Heritable Disease Links Cancer to Aging

To understand how cancer might be related to aging, Jan Karlseder, assistant professor in the Molecular and Cell Biology Laboratory, analyzed genetic damage in chromosomes of patients with a heritable disease known as Werner Syndrome (WS). These patients show signs of premature aging, such as wrinkling or balding, early in life and die in midlife often due to a predisposition to cancer.

Karlseder and postdoctoral fellow Laure Crabbe reported in Proceedings of the National Academy of Sciences that sometimes the protective structures at the tips of every chromosome – called telomeres – were missing on WS patient chromosomes. When telomeres are lost or damaged, chromosomes can randomly break, leading to a condition described as genomic instability, which often precedes cancer development.

The investigators grew cells taken from WS patients in culture and artificially supplied those cells with a gene encoding an enzyme that reconstructs damaged or missing telomeres. After the cells divided several times, their DNA was re-examined for evidence of damage.

The cultured cells supplied with the telomere-building enzyme showed evidence of chromosomal repair: their telomeres had been elongated, and no chromosomal aberrations accumulated. These findings indicate a direct relationship between aging, telomere loss and cancer. Karlseder predicts that cancer seen in older adults potentially could have a similar basis as that seen in WS patients.