The pancreatic β-cell in ageing: Implications in age-related diabetes

Abstract

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt fi-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity. However, a precise understanding of the pancreatic fi-cell response in ageing is still lacking. In this review, we summarize the age-related alterations, adaptations and/or failures of fi-cells at the molecular, morphological and functional levels in mouse and human. Age-associated alterations include processes such as fi-cell proliferation, apoptosis and cell identity that can influence fi-cell mass. Age-related changes also affect fi-cell function at distinct steps including electrical activity, Ca2+ signaling and insulin secretion, among others. We will consider the potential impact of these alterations and those mediated by senescence pathways on fi-cells and their implications in age-related T2D. Finally, given the great diversity of results in the field of fi-cell ageing, we will discuss the sources of this heterogeneity. A better understanding of fi-cell biology during ageing, particularly at older ages, will improve our insight into the contribution of fi-cells to ageassociated T2D and may boost new therapeutic strategies.