Figure 1.

The seven pillars of aging in the context of neuronal and axonal degeneration. Each pillar associated to the aging process is represented in a colored box. Most relevant pathways and molecules misregulated during aging are highlighted in each box, altogether with the consequences in neuronal senescence and axonal degeneration. A misregulated response to macromolecular damage and inflammation lead to increased ROS and a decrease in available NAD⁺, triggering axonal degeneration. Aging also decreases the number of neuronal stem cells (NSCs) and their regenerative capability. Caloric restriction works in a protective way against aging with a mechanism opposite to the one observed with the age-linked disruption of circadian rhythm. Altered DNA modification and repair trigger pro-senescence phenotypes that lead to neuronal death, same phenotype induced by decrease of response to stress stimuli and oxidative damage.