To cite just a few examples, many of the positive effects of exercise depend on the concomitant increases of BDNF (Marosi and Mattson, 2014) and IGF1 levels (Llorens-Martin et al., 2009), as well as calorie restriction interacts with the individual's activity level (Mattson, 2000; Dietrich and Horvath, 2012), while high levels of BDNF and IGF1 may induce negative effects on the brain (Gwag et al., 1995; Ramsden et al., 2003) and the energy intake is associated to the risk of developing neurodegenerative diseases in a biphasic dose-response. The gene discussed is IGF1; the disease is neurodegenerative disease.