The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation

Cnop, M.; Hughes, S.J.; Igoillo-Esteve, M.; Hoppa, M.B.; Sayyed, F.; Laar, L. van de; ... ; Clark, A. (2010)

Article / Letter to editor

Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents < 1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years. LB content was determined by electron microscopical morphometry in sections of beta cells from human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n = 10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was estimated by three-dimensional (3D) mathematical modelling. LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in mouse < 10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from a parts per thousand yen90% (< 10 years) to a parts per thousand yen97% (> 20 years) and remained constant thereafter. Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.

• Ageing Human Islet Longevity Mathematical modelling Monkey Mouse Neogenesis Pancreatic beta cell Type 2 diabetes low-density-lipoprotein oxidative stress partial-pancreatectomy insulin-secretion mass age proliferation regeneration apoptosis birth

• All authors: Cnop, M.; Hughes, S.J.; Igoillo-Esteve, M.; Hoppa, M.B.; Sayyed, F.; Laar, L. van de; Gunter, J.H.; Koning, E.J.P. de; Walls, G.V.; Gray, D.W.G.; Johnson, P.R.V.; Hansen, B.C.; Morris, J.F.; Pipeleers-Marichal, M.; Cnop, I.; Clark, A.
• Date: 2010-02-28
• Journal: Diabetologia
• Volume: 53
• Issue: 2
• Pages: 321 - 330
• DOI: doi:10.1007/s00125-009-1562-x