Seminar in Biological Mechanisms of Aging and Cancer/Altered intercellular communication

Altered intercellular communications is defined as changes in endocrine, neuroendocrine, or neuronal pathways that lead to mechanisms of aging[1]. One intercellular pathway that effects aging is the inflammatory pathway. This inflammatory response is know to have an effect on many age related diseases like diabetes and atherosclerosis. As the inflammatory response increases with age, it's closely related neurohormonal pathway is downregulated further contributing to the affects of aging [1].

Research done by Zhang et. al investigated these pathways more in the hypothalmus. This pathway involves the nuclear factor κB (NF-κB) pathway and how it affects Gonadotropin releasing hormone (GnRH) to promote aging. It is seen that NF-κB activity in the mediobasal hypothalmus (MBH) increases with age. Upon activation of NF-κB with IKK-β it showed a direct decrease in the lifespan of mice, however, with the inhibition of NF-κB using IκB-α there was an increase in lifespan as well as improved muscle endurance and cognitive functioning. IKK-Β and NF-κB were found to inhibit the GnRH promoter and it's release from neurons. This effect is seen in the MBH when it is injected with these factors. This effect also traveled to the dentate gyrus signifying more intercellular communication to different parts of the brain. When GnRH is underexpressed signs of aging occur, however the study showed that with increased levels of hormone the effects of aging are diminished significantly[2]. This study directly represents how alterations in cellular communication can affect aging.

This is a graphical abstract of the IKK-β and NF-κB pathway and how it affects old age starting in the hypothalamus. Based off of an article written by Zhang, G. et. al (2013).
  1. 1.0 1.1 López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
  2. Zhang, G., Li, J., Purkayastha, S., Tang, Y., Zhang, H., Yin, Y., ... & Cai, D. (2013). Hypothalamic programming of systemic ageing involving IKK-[bgr], NF-[kgr] B and GnRH. Nature, 497(7448), 211-216.