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
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Mentions: To investigate age-associated changes of NMNAT2 vesicles in peripheral axons, we imaged and quantified the axonal transport of NMNAT2-Venus particles in sciatic nerve axons (Fig 1A). Average (total displacement of a particle/time tracked) and maximal (farthest displacement of each tracked particle between 2 frames) particle velocities in both anterograde and retrograde directions remained stable from 1.5 and 18 months, but then reduced significantly in animals at 24 months of age (Fig 1B and C). Surprisingly, the number of particles observed moving anterogradely and retrogradely showed a significant drop even in young animals between the ages of 3 and 6 months. This was followed by a relatively stable plateau that was maintained at least up to 18 months. From 18 to 24 months, another significant reduction in the number of anterogradely moving particles was observed, along with a similar, but statistically nonsignificant trend in the retrograde direction (Fig 1D and E). To test whether these changes could have been caused by changes in expression level of the transgene over the lifetime of the animals, which might impair tracking of particles, we quantified the average fluorescence intensity of labeled axons from animals of different ages. As shown in Table 3, there were no consistent trends or differences in fluorescence intensity that would explain the observed changes in the number of moving particles.
Affiliation: Signalling ISP, The Babraham Institute, Babraham Research Campus, Cambridge, UK.