Researchers here investigate the mechanisms involved in thymic involution, the atrophy of the thymus that occurs early in adulthood. The scientists propose that this atrophy occurs because thymus tissue is deficient in natural antioxidant compounds, and is thus unable to resist even normal levels of oxidative stress in the body.
The thymus plays an essential role in the process of generating new immune cells to tackle threats such as viruses, bacteria, and rogue cells. In childhood this organ is very active, but in adult life the flow of new immune cells slows to a trickle as a result of atrophy of the thymus. This is one of the factors contributing to the age-related decline of the immune system, and a number of research groups are investigating ways to rejuvenate or replace the thymus so as to provide a larger supply of active, useful immune cells to adults. This research on the cause of thymic involution is probably less relevant to rejuvenation, as the damage is already done in those of us needing a new thymus, but it may be useful when it comes to the ongoing protection and maintenance of a rejuvenated or replaced thymus.
The development of interventions to slow the progression of thymus atrophy has been limited by the lack of knowledge about the underlying mechanisms. The prevailing theory suggests that sex hormones play a key role, but this explanation does not account for the accelerated speed at which the thymus diminishes in size in comparison to other tissues. Researchers developed a computational approach for analyzing the activity of genes in two major thymic cell types - stromal cells and lymphoid cells - in mouse tissues, which are very similar to human thymic tissues in terms of function and the properties of atrophy. They found that stromal cells were deficient in an antioxidant enzyme called catalase, resulting in the accumulation of free radical and metabolic damage.
To test whether catalase deficiency plays a causal role in thymus atrophy, the researchers performed genetic experiments to enhance catalase levels in mice. By 6 months of age, the size of the thymus of the genetically engineered mice was more than double that of normal mice. Moreover, mice that were treated with two common antioxidants from the time of weaning achieved nearly normal thymus size by 10 weeks of age. "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."
Taken together, the findings provide support for the free-radical theory of aging, which proposes that reactive oxygen species such as hydrogen peroxide cause cellular damage that contributes to aging and a variety of age-related diseases. These toxic molecules, which form in cells as a natural byproduct of the metabolism of oxygen, have been linked to progressive atrophy in many organs and tissues as part of the normal aging process. However, these are generally slow, progressive processes that do not become apparent until late in life and often go mostly unnoticed.