title: Longevity of human islet α- and β-cells.
abstract: 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 α- and β-cells in adults; cell populations in rodents respond to increased secretory demand in obesity (30-fold β-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 β-cells in humans >20-30 years has been shown by (14) C 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 D3 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 β-cell population was established by the age of 20. New data show that human α-cell lipofuscin content is less than that seen in β-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.
authors.affiliation: Laboratory of Experimental Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Cnop
authors.forename: M
authors.initials: M
authors.lastname: Igoillo-Esteve
authors.forename: S J
authors.initials: SJ
authors.lastname: Hughes
authors.forename: J N
authors.initials: JN
authors.lastname: Walker
authors.forename: I
authors.initials: I
authors.lastname: Cnop
authors.forename: A
authors.initials: A
authors.lastname: Clark
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D002455:Cell Division; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008062:Lipofuscin / Q000378:metabolism*; D051379:Mice
chemical_list: D001786:Blood Glucose; D008062:Lipofuscin