Pathways regulating cell senescence and cell cycle underlie many processes associated with ageing and age-related pathologies, and they also mediate cellular responses to exposure to stressors. Meanwhile, there are central mechanisms of the regulation of stress responses that induce/enhance or weaken the response of the whole organism, such as hormones of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic and parasympathetic systems, thymic hormones, and the pineal hormone melatonin. Although there are many analyses considering relationships between the HPA axis and organism ageing, we found no systematic analyses of relationships between the neuroendocrine regulators of stress and inflammation and intracellular mechanisms controlling cell cycle, senescence, and apoptosis. Here, we provide a review of the effects of neuroendocrine regulators on these mechanisms. Our analysis allowed us to postulate a multilevel system of central regulators involving neurotransmitters, glucocorticoids, melatonin, and the thymic hormones. This system finely regulates the cell cycle and metabolic/catabolic processes depending on the level of systemic stress, stage of stress response, and energy capabilities of the body, shifting the balance between cell cycle progression, cell cycle stopping, senescence, and apoptosis. These processes and levels of regulation should be considered when studying the mechanisms of ageing and the proliferation on the level of the whole organism.

Modulation of autoimmune inflammation by the thymic peptides thymulin and thymopentin was studied in mice with acute experimental autoimmune encephalomyelitis (EAE), which resembles multiple sclerosis in humans. EAE was induced in NZW mice by a single immunisation with myelin basic protein coupled with adjuvants. Visible signs of pathology appeared on days 12-14 after the immunisation, peaked on days 20-25, were retained up to day 45, and then reverted. A biphasic cytokine response was also detected. In the "early" phase, which started at day 35, increased levels of interferon-gamma and interleukin-6 in the blood were observed; during the "delayed" phase, which started at day 48, the levels of plasma interleukin-17 and tumour necrosis factor-alpha were also raised. In addition, the phosphorylation of NF-kappaB signalling proteins and the production of heat shock protein Hsp72 were significantly increased in splenic lymphocytes from EAE-bearing mice. When applied intraperitoneally every other day for 30 days, either thymulin or thymopentin (15 μg per 100g of body weight) significantly reduced the disease severity compared to untreated EAE mice. The effect of thymulin but not thymopentin remained after its withdrawal. Thymulin reduced the cytokine response in both the early and the delayed phases, whereas thymopentin only reduced the "early phase cytokines" (IL-6 and interferon-gamma). Both peptides significantly reduced the level of phosphorylation of the NF-kappaB signalling protein IKK and the production of Hsp72 protein. The data presented here indicate the presence of time-dependent immune responses in EAE-bearing mice, which may be associated with the Th1 and Th17 subpopulations of T-cells. Thymulin and thymopentin demonstrated different patterns of activity, most likely via mechanisms involved in NF-kappa B signalling and Hsp72 expression.