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Enzyme Deletion Preserves Thymus Function, Extends Lifespan

Researchers have shown, in a mouse model, that deletion of the gene for a particular enzyme [pregnancy-associated plasma protein A (PAPPA)] can preserve thymus function throughout life and extend lifespan by as much as 30 percent. The so-called PAPPA “knockout” mice also showed a significantly lower occurrence of spontaneous tumors than typical mice. It is suggested that preservation of thymus function permits the mice to maintain a robust immune system that contributes to healthy longevity. In all normal mammals, the thymus―the organ that produces T-cells to fight disease and infection―degenerates with age. PAPPA controls the availability in tissues of a hormone known as insulin-like growth factor (IGF) that is a promoter of cell division. Hence, IGF is required for normal embryonic and postnatal growth. But IGF also is associated with tumor growth, inflammation, and cardiovascular disease in adults. By deleting PAPPA, the researchers were able to control the availability of IGF in tissues and dampen its many ill effects. In the thymus, deletion of PAPPA maintained just enough IGF to sustain production of T cells without consuming precursor cells, thereby preventing the degeneration of the thymus. "Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to maintain immune protection throughout life," study leader Dr. Abbe de Vallejo said. "This study has profound implications for the future study of healthy aging and longevity." The results were published in the July 7 issue of PNAS. [Press release] [PNAS article]