Hypothesis: involution of the thymus with aging--programmed and beneficial

Abstract

This is an attempt to find a teleological rationale for the involution of the thymus with aging. The thymus is the first organ in the body to age, which seems incongruent considering its cardinal role in the immune system. An analogical incongruency can be seen in the fact that acute stress is generally accompanied by a reversible involution of the thymus. We hypothesized earlier, that this reversible involution might protect the organism from the danger of autoimmune diseases. It stands to reason that, in nature, conditions leading to stress frequently entail massive tissue destruction. This may cause the appearance of "altered self" components, leading to the formation of autoantibodies. Hence, the temporary shut-off of thymic activity would be beneficial. A similar argument holds in the case of aging and will be elaborated as follows: 1) Formation of antibodies per se entails the danger of autoimmune mechanisms, hence the process is controlled at various levels; 2) The aging process is characterized by the increasing appearance of non-self components as a result of DNA errors and post-translational changes due to free radicals and other high energy oxygen derivatives; 3) Early involution serves, in our opinion, to reduce the risk of autoimmune diseases which increases with aging, and should therefore be regarded as an adaptation of the organism to aging; 4) If this notion proves to be correct the desirability of restoring full thymic activity in old people becomes questionable.