The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
Abstract
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 halflife 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 (nondiabetic, n = 45; type 2 diabetic, n = 10) and nonhuman primates (n = 10; 5–30 years) and from 15 mice aged 10–99 weeks. Total cellular LB content was estimated by threedimensional (3D) mathematical modelling.
Results
LB area proportion was significantly correlated with age in human and nonhuman primates. The proportion of human LBpositive 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 LBpositive human beta cells (representing aged cells) increased from ≥90% (<10 years) to ≥97% (>20 years) and remained constant thereafter.
Conclusions/interpretation
Human beta cells, unlike those of young rodents, are longlived. 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.
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 Title
 The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation
 Journal

Diabetologia
Volume 53, Issue 2 , pp 321330
 Cover Date
 201002
 DOI
 10.1007/s001250091562x
 Print ISSN
 0012186X
 Online ISSN
 14320428
 Publisher
 SpringerVerlag
 Additional Links
 Topics
 Keywords

 Ageing
 Human
 Islet
 Longevity
 Mathematical modelling
 Monkey
 Mouse
 Neogenesis
 Pancreatic beta cell
 Type 2 diabetes
 Industry Sectors
 Authors

 M. Cnop ^{(1)}
 S. J. Hughes ^{(2)}
 M. IgoilloEsteve ^{(1)}
 M. B. Hoppa ^{(3)}
 F. Sayyed ^{(3)} ^{(9)}
 L. van de Laar ^{(10)} ^{(3)}
 J. H. Gunter ^{(11)} ^{(3)}
 E. J. P. de Koning ^{(12)} ^{(3)}
 G. V. Walls ^{(4)}
 D. W. G. Gray ^{(2)}
 P. R. V. Johnson ^{(2)}
 B. C. Hansen ^{(5)}
 J. F. Morris ^{(6)}
 M. PipeleersMarichal ^{(7)}
 I. Cnop ^{(8)}
 A. Clark ^{(3)}
 Author Affiliations

 1. Laboratory of Experimental Medicine and Division of Endocrinology, Université Libre de Bruxelles, Brussels, Belgium
 2. DRWF Islet Isolation Facility, Nuffield Department of Surgery, Churchill Hospital, Oxford, UK
 3. Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Oxford, OX3 7LJ, UK
 9. Department of Surgery, Leicester Royal Infirmary, Leicester, UK
 10. Department of Gastroenterology and Hepatology, Erasmus University, Rotterdam, The Netherlands
 11. Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia
 12. Department of Nephrology C3P, Leiden University Medical Center, Leiden, The Netherlands
 4. Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK
 5. Obesity, Diabetes and Aging Research Center, College of Medicine, University of South Florida, Tampa, FL, USA
 6. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK
 7. Diabetes Research Centre, Vrije Universiteit Brussel, Brussels, Belgium
 8. Department of Mathematics, Vrije Universiteit Brussel, Brussels, Belgium