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Review
. 2023 Sep 4;12(9):1205.
doi: 10.3390/biology12091205.

Interaction between Autophagy and Senescence in Pancreatic Beta Cells

Francesko Hela  1 , Cristina Aguayo-Mazzucato  1
Affiliations
Review

Interaction between Autophagy and Senescence in Pancreatic Beta Cells

Francesko Hela et al. Biology (Basel). .

Abstract

Aging leads to an increase in cellular stress due to the fragility of the organism and the inability to cope with it. In this setting, there is a higher chance of developing different cardiometabolic diseases like diabetes. Cellular senescence and autophagy, both hallmarks of aging and stress-coping mechanisms, have gained increased attention for their role in the pathophysiology of diabetes. Studies show that impairing senescence dampens and even prevents diabetes while the role of autophagy is more contradictory, implying a context- and disease-stage-dependent effect. Reports show conflicting data about the effect of autophagy on senescence while the knowledge about this interaction in beta cells remains scarce. Elucidating this interaction between autophagy and senescence in pancreatic beta cells will lead to an identification of their respective roles and the extent of the effect each mechanism has on beta cells and open new horizons for developing novel therapeutic agents. To help illuminate this relationship we will review the latest findings of cellular senescence and autophagy with a special emphasis on pancreatic beta cells and diabetes.

Keywords: SASP; beta cells; cellular senescence; diabetes; macroautophagy; senolytics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the autophagic processes in β-cells. (a) Macroautophagy, (b) chaperone-mediate autophagy, and (c) microautophagy are the three main autophagic processes that occur in β-cells. Crinophagy and vesicophagy of the insulin granules are the microautophagic mechanisms occurring only in β-cells. Figure made with BioRender.com.
Figure 2
Figure 2
Autophagic molecular mechanism. (1) Induction starts with different signals triggering the signaling cascade, leading to the formation of the isolation membrane and later of the phagophore (2). Targeted cargo and further signaling make possible phagophore elongation (3). Sealing of the double-membranous vesicle forms the mature autophagosome (4). Transportation of the mature vesicle to the vicinity of the lysosome and fusion forms the autolysosome (5). Degraded cargo is recycled back into the system and the change in nutrition state signals the modulation of autophagy through mTORC1 (6). Figure made with BioRender.com.
Figure 3
Figure 3
Role of AMPK signaling pathway in induction of autophagy and senescence. Figure made with BioRender.com.
See this image and copyright information in PMC

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