High-Fat Diet and Foetal Programming: Use of P66Shc Knockouts and Implications for Human Kind

Early life experiences can shape the developing foetus and have the potential to affect health trajectories later in life, setting the stage for healthy vs. unhealthy ageing. As an example, maternal obesity or the consumption of high-fat diet during pregnancy might act as powerful prenatal stressors, leading to adult metabolic or stress-related disorders. A growing body of evidence suggests that oxidative stress (OS) might represent a common mechanism underlying the effects of metabolic stressors affecting foetal programming and the offspring’s health outcome throughout life. In this regard, p66Shc has emerged as a mammalian gerontogene involved in the regulation of OS and in fat storage affecting health throughout life and during ageing. Knocking out this gene in mice protects from OS and from diet-induced obesity resulting overall in improved healthspan and extended longevity. Recent data, however, indicate that the role of this gene is more complex than expected and suggest that both the metabolic needs of the organism and the specific life stage might ultimately define its role.