Rodent studies of developmental programming and ageing mechanisms

Abstract

Compelling evidence exists indicating that developmental programming influences aging. Programming alters life-course phenotype in multiple organs, predisposing to diseases such as diabetes, obesity and cardiovascular disease that shorten life-span. This review describes studies in rodents, the most commonly studied species, addressing interactions of programming challenges with aging. We first consider aging and programming of insulin function that has been clearly shown to decrease with age. It is important to evaluate aging in pancreatic islets isolated from other systems. Studies discussed show premature pancreatic islet aging resulting from both maternal under- and over nutrition. New ways to determine programming of adipose tissue and effects on fat storage are explored. Oxidative stress is a major factor that regulates aging in tissues. Oxidative stress is discussed in relation to reproductive and cardiovascular aging. Premature aging is associated with both low and high glucocorticoid function. Both over and undernutrition have offspring sex specific programming effects onlife-course glucocorticoid concentrations. Evidence is provided that maternal age at conception affects offspring endocrine and metabolism aging. Finally, the importance of matching fetal nutrition and energy availability with composition and energy content in the post-weaning diet is demonstrated. This mismatch can lead to a greatly shortened life span. General principles are discussed throughout. For example, sexual dimorphism of age-related outcomes can be marked. Accelerated aging occurs early in life. Improving knowledge on programming aging interactions will improve health span as well as life span. Finally, there are considerable similarities in outcomes programmed by maternal undernutrition and overnutrition.