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“Gene chip” studies of aging genes

When hair turns gray and skin loses its youthful elasticity it is because a certain set of genes have either stopped working or are working differently. Identifying which genes function differently as people grow older is critical to understanding and treating age related diseases like Alzheimer’s, osteoporosis, rheumatoid arthritis, gum disease, and cancer.

Researchers have used a "gene chip" to simultaneously study the activity of more than 6000 genes. The study included a seven year-old, a nine year-old, two 37 year-olds, and three people in their 90s. They also studied the gene activity in three children with progeria—a disease in which children age rapidly and die of age related diseases in their teens. Researchers found that 61 of the genes increased or decreased their activity by at least two-fold by age 37. The work was done by scientists at the Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation California and is published in the March 31 issue of Science.

About one quarter of these genes maintain the DNA and ensure normal cell division. If the DNA is not quality-checked before it divides to produce two new copies, it passes on damaged genetic material to future generations of cells. The researchers found that in very old people and children with progeria, genes needed to produce healthy, high fidelity copies of cells were functioning at levels between two and twelve-fold less than healthy children and adults in their late thirties. This led to a build-up of DNA mutations and cells with abnormal numbers of chromosomes.

Genes involved with bone formation, inflammation, muscle and kidney function were also found to behave differently after middle age. For example, the activity of a gene involved with bone formation, osteoblast specific factor 2, which is linked to the onset of diseases like osteoporosis, was seven fold less in 90 year olds. A gene associated with rheumatoid arthritis was found to function at higher levels in older people.

Understanding the mechanisms of aging may inspire the development of drugs that mimic the activity of some of these genes and postpone the onset of many diseases.

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Ly, D.H. et al. Mitotic misregulation and human aging. Science 287, 2486-2492 (March 31, 2000).

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