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Aging Cell. 2018 Apr;17(2). doi: 10.1111/acel.12726. Epub 2018 Feb 4.

α-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and mice.

Author information

1
Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
2
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA, USA.
3
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
4
SoBran, Inc., Burtonsville, MD, USA.
5
Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.

Abstract

Motor function deteriorates with advancing age, increasing the risk of adverse health outcomes. While it is well established that skeletal muscles and neuromuscular junctions (NMJs) degenerate with increasing age, the effect of aging on α-motor neurons and their innervating synaptic inputs remains largely unknown. In this study, we examined the soma of α-motor neurons and innervating synaptic inputs in the spinal cord of aged rhesus monkeys and mice, two species with vastly different lifespans. We found that, in both species, α-motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin. Interestingly, the lipofuscin profile varied considerably, indicating that α-motor neurons age at different rates. Although the rate of aging varies, α-motor neurons do not atrophy in old age. In fact, there is no difference in the number of motor axons populating ventral roots in old mice compared to adult mice. Moreover, the transcripts and proteins associated with α-motor neurons do not decrease in the spinal cord of old mice. However, in aged rhesus monkeys and mice, there were fewer cholinergic and glutamatergic synaptic inputs directly abutting α-motor neurons, evidence that aging causes α-motor neurons to shed synaptic inputs. Thus, the loss of synaptic inputs may contribute to age-related dysfunction of α-motor neurons. These findings broaden our understanding of the degeneration of the somatic motor system that precipitates motor dysfunction with advancing age.

KEYWORDS:

aging; alpha-motor neuron; lipofuscin; neurodegeneration; spinal cord; synapse

PMID:
29397579
PMCID:
PMC5847869
DOI:
10.1111/acel.12726
[Indexed for MEDLINE]
Free PMC Article

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