CENP-A, a protein required for chromosome segregation in mitosis, declines with age in islet but not exocrine cells.
Beta-cell replication dramatically declines with age. Here, we report that the level of CENP-A, a protein required for cell division, declines precipitously with age in an islet-specific manner. CENP-A is essentially undetectable after age 29 in humans. However, exocrine cells retain CENP-A expression. The decline in islet-cell CENP-A expression is more striking in humans than in mice, where CENP-A expression continues to be detectable at low levels even in elderly mice. The mechanism by which CENP-A declines appears to be post-transcriptional, as there was no correlation between CENP-A mRNA levels and age or islet purity. This finding has implications for efforts to induce beta-cell replication as a treatment for diabetes.
Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Seung-Hee
SH
Lee
Pamela
P
Itkin-Ansari
Fred
F
Levine
D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D005333:Fetus / Q000033:anatomy & histology; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D046790:Pancreas, Exocrine / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism
D001324:Autoantigens; C000619700:CENPA protein, human; C000619701:Cenpa protein, mouse; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D012333:RNA, Messenger