Axonal transport declines with age in two distinct phases separated by a period of relative stability.
Bottom Line: 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.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.
Affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.Show MeSH
Related in: MedlinePlus
Mentions: The significant drop in transport rates of NMNAT2-Venus particles observed from 3 to 6 months of age prompted us to ask whether this was a general effect on multiple fast axonal transport cargoes, or perhaps a more specific effect on NMNAT2 vesicles. To start addressing this question, we imaged mitochondrial transport in sciatic nerves of MitoS mice expressing mitochondrially targeted CFP under the same Thy1.2 promoter (Fig 2A). We previously reported a fall in axonal transport in these mice between 8 and 24 months (Gilley et al., 2012), but earlier ages have not been studied. Here, we observed a significant drop in the number of anterogradely and retrogradely transported mitochondria from 3 to 6 months of age, with no further change until at least 12 months (Fig 2B and C). Over the same time course, no significant changes in transport velocities were observed (Fig 2D and E). As for NMNAT2-Venus above, changes in the average fluorescence intensity of labeled axons are unlikely to account for these differences (Table 3). These findings parallel the results for NMNAT2-Venus above and suggest a general reduction in fast axonal transport rates in peripheral nerves between 3 and 6 months of age, followed by a more stable plateau during adult life. Combined with our findings in older MitoS mice (Gilley et al., 2012), these results suggest 2 major periods of reduction in the fast axonal transport of several cargoes, 1 occurring in young animals between 3 and 6 months of age, and the other during old age after 18 months.
Affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.