Biomarkers of aging in the neuroendocrine-immune domain. Time for a new theory of aging?

A common and generally accepted assumption is that with advancing age, the thymus undergoes progressive and irreversible involution. This is considered the main cause for the age-related deterioration of various immune functions and, ultimately, for the increased incidence of infectious, neoplastic, and automimmune diseases in old age. This assumption is no longer tenable because of several clear-cut demonstrations that age-related thymic involution is not an intrinsic and irreversible phenomenon. Various neuroendocrine or nutritional manipulations can to induce a regrowth of the thymus, even when applied in old age. This thymic reconstitution is followed by a consistent recovery of peripheral immune functions. These data strongly support the idea that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of such interactions in old age that is responsible for most of the age-associated dysfunctions. On the basis of this experimental and clinical evidence and as an alternative to purely immune or neuroendocrine theories of aging, a neuroendocrine-immune hypothesis is proposed. Further work is required to determine if the age-related disruption of neuroendocrine-immune interactions occurs because of progressive accumulation of stressor-dependent consequences at the level of one or the other system or if it may depend on a single common cause.