A new study reveals that thymus atrophy may stem from a decline in its ability to protect against DNA damage from free radicals. The damage accelerates metabolic dysfunction in the organ, progressively reducing its production of pathogen-fighting T cells. Common antioxidants may slow thymus atrophy and be a Rx strategy for protecting elderly from infections.
“The thymus ages more rapidly than any other tissue in the body, diminishing the ability of older individuals to respond to new immunologic challenges, including evolving pathogens and the vaccines that may otherwise offer protection from them,” says Howard Petrie of SRI. Starting around puberty, the thymus rapidly decreases in size and loses capacity to produce enough new T cells. This loss is partially offset by the duplication of existing T cells, but the resulting population of cells becomes more and more biased toward memory T cells. So broad-spectrum immunity against new pathogens and protective immune responses elicited by new vaccines diminish with age.
Petrie and Ann Griffith developed a computational approach for analyzing the activity of genes in 2 major thymic cell types- stromal cells and lymphoid cells – in mouse tissues – v. similar to human thymic tissues. The stromal cells were deficient in an antioxidant enzyme called catalase, resulting in the accumulation of free radical and metabolic damage.
They enhanced catalase levels in mice. By 6 months of age, the size of the thymus of the genetically engineered mice was >double that of normal mice + mice treated with 2 common antioxidants from the time of weaning achieved nearly normal thymus size by 10 wks.
The findings support free-radical theory of aging: ie reactive oxygen species eg H2O2 cause cellular damage that contributes to aging and a variety of age-related diseases. These toxic molecules, natural byproduct of metabolism of oxygen, is linked to progressive atrophy in many organs and tissues as part of the normal aging process.
>> “In the case of the thymus, atrophy is more rapid than other tissues, … a consequence of stromal catalase deficiency in the context of a highly metabolic environment designed to support the demands of T-cell proliferation,” Petrie says. “Our studies show that, rather than an idiosyncratic relationship to sex steroids, thymic atrophy represents the widely recognized process of accumulated cellular damage resulting from lifelong exposure to the oxidative byproducts of aerobic metabolism.” In future studies, the researchers will investigate whether antioxidant supplementation improves the functioning of the thymus and the immune system during aging. http://www.eurekalert.org/pub_releases/2015-08/cp-rao073015.php
The thymus exhibits accelerated atrophy with age due to changes in stromal cells •Global transcriptome analysis reveals that stromal cells are deficient in catalase •Stromal cells showed elevated H2O2 levels and multiple hallmarks of oxidative damage •Genetic or biochemical restoration of antioxidant activity ameliorates thymic atrophy
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