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

Arrojo e Drigo, R.; Erikson, G.; Tyagi, S.; Capitanio, J.; Lyon, J.; Spigelman, A.; Bautista, A.; Manning Fox, J. E.; Shokhirev, M.; MacDonald, P.; Hetzer, M.

doi:10.1101/729541

bioRxiv · 10.1101/729541

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

Arrojo e Drigo, R.·Erikson, G.·Tyagi, S.·Capitanio, J.·Lyon, J.·Spigelman, A.·Bautista, A.·Manning Fox, J. E.·Shokhirev, M.·MacDonald, P.·Hetzer, M.

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Abstract

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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Arrojo e Drigo, R., Erikson, G., Tyagi, S., Capitanio, J., Lyon, J., Spigelman, A., Bautista, A., Manning Fox, J. E., Shokhirev, M., MacDonald, P., Hetzer, M.. 2019-08-08. Aging of human endocrine pancreatic cell types is heterogeneous and sex-specific. https://doi.org/10.1101/729541

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