title: Axonal transport declines with age in two distinct phases separated by a period of relative stability.
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.
authors.affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Milde
authors.affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Adalbert
authors.affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
authors.forename: M Handan
authors.initials: MH
authors.lastname: Elaman
authors.affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK. Electronic address: michael.coleman@babraham.ac.uk.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Coleman
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D057054:Molecular Imaging; D009416:Nerve Regeneration; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000502:physiology; D061848:Optical Imaging; D010525:Peripheral Nerves / Q000378:metabolism; D013979:Tibial Nerve / Q000502:physiology
chemical_list: D009612:Nicotinamide-Nucleotide Adenylyltransferase; C579543:Nmnat2 protein, mouse
keywords: Aging; Axon regeneration; Axonal transport; Fluorescence live imaging; Mitochondrial transport; Nicotinamide mononucleotide Adenylyltransferase 2