The deterioration in immune function that occurs as an individual ages is thought to occur because the thymus involutes with age, causing a dramatic decrease in T cell output. New data generated by Dennis Taub and colleagues from the National Institutes of Health, Baltimore, suggest that in mice, thymic involution is caused by a decrease upon aging in thymic expression of both a hormone that is better known as a stimulator of food intake (ghrelin) and its receptor. These results led them to caution that care should be taken when considering blocking ghrelin as a potential approach for treating individuals who are obese and to suggest that harnessing this pathway might provide a new approach to boost immune function in individuals who are elderly or immunocompromised.
The physiological relevance of the decrease, with age, in expression in the mouse thymus of both ghrelin and its receptor was highlighted by the observation that infusion of ghrelin into old, but not young, mice markedly increased thymic mass, improved thymic architecture, and increased thymocyte and thymic epithelial cell numbers. These changes were associated with increased T cell output and increased diversity of the TCR repertoire of the peripheral T cell population. Consistent with these observations, age-associated thymic involution was accelerated in mice lacking either ghrelin or its receptor.