Aim/hypothesis
Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number
is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed
with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta
cells, which might in turn contribute to the age-related decline in insulin secretory capacity.
Methods
We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years.
Islets (n = 20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted
mtDNA (%), which were determined using real-time PCR methods.
Results
There was a significant negative correlation between mtDNA copy number and islet donor age (r = –0.53, p = 0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged ≥50 years (n = 8) compared with those aged <50 years (n = 7) (median [interquartile range]: 418 [236–503] vs 596 [554–729] mtDNA copy number/diploid genome; p = 0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc.
Conclusion/interpretation
Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number
that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell
insulin secretory capacity.
Keywords Ageing - Human islets - Mitochondrial DNA copy number - Mitochondrial DNA deletion - Mitochondrial DNA depletion - Pancreatic beta cell function
L.M. Cree and S.K. Patel contributed equally to this study.