Macroautophagy and normal aging of the nervous system: Lessons from animal models

Authors:

Emmanouela Kallergi1 and Vassiliki Nikoletopoulou1
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Affiliations:

1 University of Lausanne, Department of Fundamental Neurosciences, Lausanne, Switzerland.

Keywords: 

proteostasis, macroautophagy, nervous system, aging.

Abbreviatons:

AgRP - Agouti-related protein;

AMPA – α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;

AV – autophagic vesicle;

CMA – chaperone-mediated autophagy;

dFP – dual fluorescent protein;

DG – dentate gyrus;

ER – endoplasmic reticulum;

LTD – long-term depression;

MB – mushroom body;

mFP – monomeric fluorescent protein;

MSH – melanocyte-stimulating hormone;

mTOR – mammalian target of rapamycin;

NMDA – N-methyl-D-aspartate;

POMC – proopiomelanocortin;

UPS – ubiquitin-proteasome system;

v-ATPase – vacuolar ATPase.

Corresponding Author(s):

Vassiliki Nikoletopoulou, University of Lausanne, Department of Fundamental Neurosciences, Lausanne, Switzerland; vassiliki.nikoletopoulou@unil.ch

Conflict of interest statement:

The authors declare no conflicts of interest.

Please cite this article as:

Emmanouela Kallergi and Vassiliki Nikoletopoulou (2021). Macroautophagy and normal aging of the nerv-ous system: Lessons from animal models. Cell Stress 5(10): 146-166. doi: 10.15698/cst2021.10.257

© 2021 Kallergi and Nikoletopoulou. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and re-production in any medium, provided the original author and source are acknowledged.

Abstract:

Aging represents a cumulative form of cellular stress, which is thought to challenge many aspects of proteostasis. The non-dividing, long-lived neurons are particularly vulnerable to stress, and, not surprisingly, even normal aging is highly associated with a decline in brain function in humans, as well as in other animals. Macroautophagy is a fundamental arm of the proteostasis network, safeguarding proper protein turnover during different cellular states and against diverse cellular stressors. An intricate interplay between macroautophagy and aging is beginning to unravel, with the emergence of new tools, including those for monitoring autophagy in cultured neurons and in the nervous system of different organisms in vivo. Here, we review recent findings on the impact of aging on neuronal integrity and on neuronal macroautophagy, as they emerge from studies in invertebrate and mammalian models.