Strategies to Overcome Neuroendocrine Immune Deficits in Aging: Role of Neuroendocrine-Immune Modulators and Bioactive Plant Extracts

The neuroendocrine immune network functions in a delicate balance during health and the ability to maintain this balance through disease affects the outcome of the disease. During aging, there is a general decline in each of these systems that reflects on their synergistic functions and affect homeostasis leading to age-associated diseases including cancer, autoimmunity and degenerative diseases. Immunomodulation by estrogen through cyclic menstrual variations and precipitous decline during reproductive aging, facilitates the development of several female-specific age-associated diseases such as autoimmunity, osteoporosis, cardiovascular diseases and hormone-dependent cancers. Centrally and peripherally, norepinephrine released from sympathetic innervation of lymphoid organs plays a key role in naïve T-cell regulation. Hypothalamic catecholaminergic networks play a crucial role in endocrine regulation and indirectly affect immune functions during health and disease. Immune mediators such as cytokines can cross the blood brain barrier and bind to central neurons eliciting sickness behaviour and facilitate reprogramming of energy reserves to be used to fight the disease. Monoamine oxidase inhibitors like deprenyl and synthetic drugs like donepezil have been shown to exert positive effects on the age-associated decline in the neuroendocrine-immune network by delaying peripheral degeneration and increasing immune functions. Similar beneficial effects have been observed in vitro and in vivo in rats treated with Brahmi (Bacopa monnieri) and Noni (Morinda citrifolia). Comparative analysis of the strategies for reversing age-associated immunosenescence using synthetic drugs and natural remedies have shown significant immunomodulatory effects in middle-aged and old rats through modulation of MAPK and NF-kB signaling cascades.