Enzyme that Promotes Strong Immune Response and Longevity Identified

The key to longevity may lie in an enzyme with the ability to promote a strong immune system into old age by maintaining the function of the thymus throughout life, according to researchers studying an "anti-aging” mouse model that lives longer than a typical mouse.

The study, led by Abbe de Vallejo, Ph.D., associate professor of pediatrics and immunology at the University of Pittsburgh School of Medicine (UPMC; PA, USA) and immunologist at Children's Hospital of Pittsburgh of UPMC, reported that the novel mouse model has a thymus that remains intact throughout its life. In all mammals, the thymus--the organ that produces T cells to combat disease and infection--degenerates with age.


Results of the study were published in this the July 10, 2009, issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS). "These findings give us hope that we may one day have the ability to restore the function of the thymus in old age, or perhaps by intervening at an early age, we may be able to delay or even prevent the degeneration of the thymus in order to maintain our immune defenses throughout life,” said Dr. de Vallejo.

The mouse model that Dr. de Vallejo's team evaluated was developed by his colleague Cheryl Conover, Ph.D., endocrinology researcher at the Mayo Clinic (Rochester, MN, USA). In this knockout mouse model, researchers deleted an enzyme known as pregnancy-associated plasma protein A (PAPPA). PAPPA-knockout mice live at least 30% longer and have significantly lower occurrence of spontaneous tumors than typical mice.

PAPPA controls the availability in tissues of a hormone known as insulin-like growth factor (IGF) that is a promoter of cell division. Therefore, IGF is essential 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 deleterious 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,” Dr. de Vallejo noted. "This study has profound implications for the future study of healthy aging and longevity.”

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