PAPPA, Mouse Longevity, and the Thymus

Researchers here investigate the effects of a mouse longevity gene, and see that it promotes a better functioning thymus and immune system in old age: "Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). ... deletion of PAPPA in mice leads to lifespan extension. ... Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA(-/-) mice maintain [a thymus] densely populated by [thymocytes] that are capable of differentiating into single-positive CD4 and CD8 T cells. ... PAPPA(-/-) mice have an overall larger pool of naive T cells ... old PAPPA(-/-) mice have significantly lower prevalence of [T cell forms] known to inhibit T cell activation with normal aging. ... These data suggest [a relationship between IGF and the immune system in healthy longevity]. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to [maintain the immune system during] aging." Reversing the decline of the aging immune system is an important step in prolonging healthy life; the more potential strategies on the table, the better off we are.


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