Rodent studies of developmental programming and ageing mechanisms: Special issue: In utero and early life programming of ageing and disease

Elena Zambrano, Consuelo Lomas-Soria, Peter W. Nathanielsz

Research output: Contribution to journalReview articlepeer-review

Abstract

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

Original languageEnglish (US)
Article numbere13631
JournalEuropean Journal of Clinical Investigation
Volume51
Issue number10
DOIs
StatePublished - Oct 2021
Externally publishedYes

Keywords

  • ageing
  • developmental programming
  • metabolism
  • oxidative stress
  • rodents
  • sexual dimorphism

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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