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Axonal transport declines with age in two distinct phases separated by a period of relative stability.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Milde, Stefan 
Adalbert, Robert 
Elaman, M Handan 
Coleman, Michael P 

Abstract

Axonal transport is critical for supplying newly synthesized proteins, organelles, mRNAs, and other cargoes from neuronal cell bodies into axons. Its impairment in many neurodegenerative conditions appears likely to contribute to pathogenesis. Axonal transport also declines during normal aging, but little is known about the timing of these changes, or about the effect of aging on specific cargoes in individual axons. This is important for understanding mechanisms of age-related axon loss and age-related axonal disorders. Here we use fluorescence live imaging of peripheral nerve and central nervous system tissue explants to investigate vesicular and mitochondrial axonal transport. Interestingly, we identify 2 distinct periods of change, 1 period during young adulthood and the other in old age, separated by a relatively stable plateau during most of adult life. We also find that after tibial nerve regeneration, even in old animals, neurons are able to support higher transport rates of each cargo for a prolonged period. Thus, the age-related decline in axonal transport is not an inevitable consequence of either aging neurons or an aging systemic milieu.

Description

Keywords

Aging, Axon regeneration, Axonal transport, Fluorescence live imaging, Mitochondrial transport, Nicotinamide mononucleotide Adenylyltransferase 2, Aging, Animals, Axonal Transport, Axons, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Molecular Imaging, Nerve Regeneration, Neurodegenerative Diseases, Nicotinamide-Nucleotide Adenylyltransferase, Optical Imaging, Peripheral Nerves, Tibial Nerve

Journal Title

Neurobiol Aging

Conference Name

Journal ISSN

0197-4580
1558-1497

Volume Title

36

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/L003813/1)