PT  - JOURNAL ARTICLE
AU  - Rafael Arrojo e Drigo
AU  - Galina Erikson
AU  - Swati Tyagi
AU  - Juliana Capitanio
AU  - James Lyon
AU  - Aliya F Spigelman
AU  - Austin Bautista
AU  - Jocelyn E Manning Fox
AU  - Max Shokhirev
AU  - Patrick E. MacDonald
AU  - Martin W. Hetzer
TI  - Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific
AID  - 10.1101/729541
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 729541
4099  - http://biorxiv.org/content/early/2019/08/08/729541.short
4100  - http://biorxiv.org/content/early/2019/08/08/729541.full
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.