Mechanisms of Ageing and Development 2002-04-30

Modulation of neuroendocrine--immune signaling by L-deprenyl and L-desmethyldeprenyl in aging and mammary cancer.

Srinivasan ThyagaRajan, David L Felten

Index: Mech. Ageing Dev. 123(8) , 1065-79, (2002)

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Abstract

The aging process is characterized by a decline in cellular functions of diverse systems of the body, including the neuroendocrine-immune network. One neuroendocrinological theory of aging is based on findings that the loss of hypothalamic neurotransmitter functions and an imbalance in hormonal secretion contribute to the cessation of reproductive cycles and the development of mammary and pituitary tumors. One potential cause of immunosenescence is an age-related decline in the regulatory functions of sympathetic noradrenergic nerve fibers whose neurotransmitters signal lymphoid cells in the bone marrow, thymus, spleen, and lymph nodes. In addition to impairment caused by the generation of free radicals during numerous biochemical processes, there is a shift in the pro-oxidant/anti-oxidant balance resulting in cellular oxidative stress and hastening the aging process. Altered interactions between the neuroendocrine system and the immune system are associated with increased incidence, development, and growth of breast cancer and other neoplastic diseases. We have demonstrated that the disruption in the neuroendocrine-immune interactions in old rats, and in female rats with mammary tumors, can be reversed by deprenyl, a monoamine oxidase inhibitor. Deprenyl treatment leads to enhanced central and peripheral catecholaminergic activity and a readjustment of immunological responses. In this brief review, the nature and changes in the bi-directional communication between the neuroendocrine system and immune system and the possible mechanism(s) of actions of deprenyl in restoring these interactions during aging and mammary cancer are discussed.