Fig. 5

Multiple communication system that includes neural, immune, endocrine, and metabolic pathways lead to degeneration. Continuous fluctuation of the microbiota due to the environment constantly influences the inflammatory, immune, and metabolic responses of the CNS [110]. With age, the permeability of intestinal and BBB is often impaired [84, 161]. The gut microbiota metabolizes and release many growths, metabolic and inflammatory factors which could penetrate the brain via the circulating blood. These substances contribute to increase the inflammatory, immune, and oxidative phenomena that exist in the elderly brain due to the accumulation over time of many abnormal proteins due to their hydrophobic conformation. The very likely origin of these malformed proteins is found in the accumulation during senescence of many mutations in post-mitotic cells that are neurons [9, 76]. In addition, the role of epigenetic dysregulation of gene expression induced by aging or abnormal environmental stimulation is also considered to be an important factor in neurodegeneration and cognitive alterations [125]. Abbreviations: BBB, blood-brain barrier; CNS, central nervous system