RT Journal Article
SR Electronic
T1 Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 729541
DO 10.1101/729541
A1 Rafael Arrojo e Drigo
A1 Galina Erikson
A1 Swati Tyagi
A1 Juliana Capitanio
A1 James Lyon
A1 Aliya F Spigelman
A1 Austin Bautista
A1 Jocelyn E Manning Fox
A1 Max Shokhirev
A1 Patrick E. MacDonald
A1 Martin W. Hetzer
YR 2019
UL http://biorxiv.org/content/early/2019/08/08/729541.abstract
AB The human endocrine pancreas must regulate glucose homeostasis throughout the human lifespan, which is generally decades. We performed meta-analysis of single-cell, RNA-sequencing datasets derived from 36 individuals, as well as functional analyses, to characterize age-associated changes to the major endocrine pancreatic cell types. Increasing age was associated with shifts in pancreatic alpha and beta cell identity and loss of nuclear integrity in non-diabetic humans. In non-diabetic individuals ≥ 50 years old, 80% of their beta cells exhibited a transcriptional signature similar to cells from type-2 diabetic (T2D) donors. Surprisingly, ∼5% of beta cells from T2D donors retained a youthful, N.D. transcriptional profile. Furthermore, beta cell function was reduced by 50% during aging in men but not women, which may explain sex-associated differences in diabetes etiology. These analyses reveal that aging of the human endocrine pancreas is sex- and cell-type specific.