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

Cnop, M., Hughes, S. J., Igoillo-Esteve, M., Hoppa, M. B., Sayyed, F., van de Laar, L., Gunter, J. H., de Koning, E. J. P., Walls, G. V., Gray, D. W. G., Johnson, P. R. V., Hansen, B. C., Morris, J. F., Pipeleers-Marichal, M., Cnop, I. and Clark, A. (2010) The long lifespan and low turnover of human islet beta cells estimated by mathematical modeling of lipofuscin accumulation. Diabetologia, 53 2: 321-330. doi:10.1007/s00125-009-1562-x


Author Cnop, M.
Hughes, S. J.
Igoillo-Esteve, M.
Hoppa, M. B.
Sayyed, F.
van de Laar, L.
Gunter, J. H.
de Koning, E. J. P.
Walls, G. V.
Gray, D. W. G.
Johnson, P. R. V.
Hansen, B. C.
Morris, J. F.
Pipeleers-Marichal, M.
Cnop, I.
Clark, A.
Title The long lifespan and low turnover of human islet beta cells estimated by mathematical modeling of lipofuscin accumulation
Journal name Diabetologia   Check publisher's open access policy
ISSN 0012-186X
1432-0428
Publication date 2010-02-01
Sub-type Article (original research)
DOI 10.1007/s00125-009-1562-x
Volume 53
Issue 2
Start page 321
End page 330
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted 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 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 ≥90% (<10 years) to ≥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.
Keyword Aging
Human
Islet
Longevity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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