Longevity of human islet α- and β-cells

Pancreatic islet cell regeneration is considered to be important in the onset and progression of diabetes and as a potential cell therapy. Current hypotheses, largely based on rodent studies, indicate continuous turnover and plasticity of alpha- and beta-cells in adults; cell populations in rodents respond to increased secretory demand in obesity (30-fold beta-cell increase) and pregnancy. Turnover and plasticity of islet cells decrease in mice within >1 year. In man, morphometric observations on postmortem pancreas have indicated that the cellular expansion is much smaller than the increased insulin secretion that accompanies obesity. Longevity of beta-cells in humans >20-30 years has been shown by C-14 measurements and bromo-deoxyuridine (BrdU) incorporation and there is an age-related decline in the expression of proteins associated with cell division and regeneration including cyclin 03 and PDX-1. Quantitative estimation and mathematical modelling of the longevity marker, cellular lipofuscin body content, in islets of subjects aged 1-84 years indicated an age-related increase and that 97% of the human beta-cell population was established by the age of 20. New data show that human alpha-cell lipofuscin content is less than that seen in beta-cells, but the age-related accumulation is similar; lipofuscin-positive (aged) cells form >= 95% of the population after 20 years. Increased turnover of cellular organelles such as mitochondria and endoplasmic reticulum could contribute to lipofuscin accumulation with age in long-lived cells. Induction of regeneration of human islet cells will require understanding of the mechanisms associated with age-related senescence.