Mammalian aging: Theoretical implications of changes in brain and endocrine systems during mid- and late-life in rats

Endocrine theories of aging have historically focused on altered peripheral or central regulatory mechanisms and, more recently, on the possibility that hormones may modulate the rate of brain aging itself. However, few systematic tests of such hypotheses have been conducted-partly due, perhaps, to a lack of clear criteria for putative endocrine mechanisms of aging. Simple criteria proposed here include: universality and similarity of fundamental patterns among mammals and detectable alterations early in mature life. Data are reviewed which indicate a possible role for elevated adrenocorticoid activity in aging of the mammalian brain. Additionally, recent data are summarized which show that, as early as mid-life in aging rats, widespread alterations occur in hypothalamic peptides and catecholamines and in peripheral endocrine systems. The pattern of these changes suggests that central and peripheral changes are linked. These findings are consistent with the view that early alterations in neural-endocrine processes may play a role in mammalian aging. Moreover, they provide possible insights into the specific nature of relevant alterations.