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Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific

Rafael Arrojo e Drigo, Galina Erikson, Swati Tyagi, Juliana Capitanio, James Lyon, Aliya F Spigelman, Austin Bautista, Jocelyn E Manning Fox, Max Shokhirev, Patrick E. MacDonald, Martin W. Hetzer
doi: https://doi.org/10.1101/729541
Rafael Arrojo e Drigo
1Molecular and Cell Biology Laboratory, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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  • For correspondence: rdrigo@salk.edu
Galina Erikson
2Integrative Genomics and Bioinformatics Core, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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Swati Tyagi
1Molecular and Cell Biology Laboratory, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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Juliana Capitanio
1Molecular and Cell Biology Laboratory, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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James Lyon
3Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G2E1
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Aliya F Spigelman
3Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G2E1
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Austin Bautista
3Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G2E1
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Jocelyn E Manning Fox
3Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G2E1
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Max Shokhirev
2Integrative Genomics and Bioinformatics Core, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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Patrick E. MacDonald
3Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Canada, T6G2E1
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Martin W. Hetzer
1Molecular and Cell Biology Laboratory, Salk Institute of Biological Studies, La Jolla, CA, USA 92037
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  • For correspondence: rdrigo@salk.edu
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Summary

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.

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Posted August 08, 2019.
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Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific
Rafael Arrojo e Drigo, Galina Erikson, Swati Tyagi, Juliana Capitanio, James Lyon, Aliya F Spigelman, Austin Bautista, Jocelyn E Manning Fox, Max Shokhirev, Patrick E. MacDonald, Martin W. Hetzer
bioRxiv 729541; doi: https://doi.org/10.1101/729541
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Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific
Rafael Arrojo e Drigo, Galina Erikson, Swati Tyagi, Juliana Capitanio, James Lyon, Aliya F Spigelman, Austin Bautista, Jocelyn E Manning Fox, Max Shokhirev, Patrick E. MacDonald, Martin W. Hetzer
bioRxiv 729541; doi: https://doi.org/10.1101/729541

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