한빛사논문
- 조회3,602
Abstract
Gregorio Valdez a , 1, Juan C. Tapia a , 1 , Hyuno Kang a , 1 , Gregory D. Clemenson Jr. b , F. H. Gage b , Jeff W. Lichtman a , 2 , and Joshua R. Sanes a , 2
aDepartment of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138; and
bLaboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037
Edited by Gerald D. Fischbach, The Simons Foundation, New York, NY, and approved June 4, 2010 (received for review February 20, 2010)
1G.V., J.C.T., and H.K. contributed equally to this work.
Abstract
The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.
aging, neuromuscular junction, muscle, motor neuron, sarcopenia
Footnotes
2To whom correspondence may be addressed.
Author contributions: G.V., J.C.T., H.K., G.D.C., F.H.G., J.W.L., and J.R.S. designed research; G.V., J.C.T., H.K., and G.D.C. performed research; G.V., J.C.T., H.K., J.W.L., and J.R.S. analyzed data; and G.V., J.C.T., H.K., J.W.L., and J.R.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at
www.pnas.org/lookup/suppl/doi:10.1073/pnas.1002220107/-/DCSupplemental.
논문정보
- Research article
- 2010년 08월 (BRIC 등록일 )
- 국외 연구진
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