September 09, 2007
Ghrelin Boosts Aging Thymus Gland

Ghrelin, which appears to stimulate appetite, also prevents or slows shrinkage of the thymus (a key organ for regulating the immune system) which occurs with increasing age.

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.

This poses a quandary: Use ghrelin which will likely increase the fat and boost the immune system? Or cut the fat and reduce the immune system? The story is actually more complex than that. See this review of how ghrelin and leptin influence appetite for the details.

This reminds me of the potential risks of older people taking growth hormone and androgens. We have a hard time trying to use hormones to boost various metabolic processes without incurring some costs of bigger problems in other areas. We need orders of magnitude more information about how human metabolism really works so that we can know how and where to intervene to achieve desired changes in metabolism without producing dangerous and unpleasant side effects.

The abstract of the paper provides a helpful clue to the ghrelin quandary. Ghrelin promotes thymopoiesis (poiesis means creation or production) during aging - but leptin (an appetite suppressor) does too.

We have previously demonstrated that the orexigenic hormone ghrelin is expressed by immune cells and regulates T cell activation and inflammation. Here we report that ghrelin and ghrelin receptor expression within the thymus diminished with progressive aging. Infusion of ghrelin into 14-month-old mice significantly improved the age-associated changes in thymic architecture and thymocyte numbers, increasing recent thymic emigrants and improving TCR diversity of peripheral T cell subsets. Ghrelin-induced thymopoiesis during aging was associated with enhanced early thymocyte progenitors and bone marrow–derived Lin–Sca1+cKit+ cells, while ghrelin- and growth hormone secretagogue receptor–deficient (GHS-R–deficient) mice displayed enhanced age-associated thymic involution. Leptin also enhanced thymopoiesis in aged but not young mice.

So maybe we could use leptin to boost thymus size without boosting appetite. Then again, maybe boosting leptin would cause problems we don't even know about yet.

Share |      Randall Parker, 2007 September 09 07:32 PM  Aging Mechanisms

Lynne Rodda said at February 20, 2008 10:51 AM:

Is there a way to test the effect of the thymus gland in an adult and if supplements or something could be taken to increase the T cell count.I have arthritis and osteoporisis. If I could increase the function of the thymus maybe the arthritis I have would get better. Any ideas?

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