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

Diabetologia. 2010 Feb;53(2):321-30. doi: 10.1007/s00125-009-1562-x. Epub 2009 Oct 24.


Aims/hypothesis: 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.

Methods: 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.

Results: 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 >or=90% (<10 years) to >or=97% (>20 years) and remained constant thereafter.

Conclusions/interpretation: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aging / physiology
  • Animals
  • Biomarkers / metabolism
  • Cause of Death
  • Cell Division
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology
  • Lipofuscin / metabolism*
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Models, Theoretical
  • Pancreas / cytology
  • Pancreas / pathology
  • Tissue Donors


  • Biomarkers
  • Lipofuscin