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Science 302 (5650): 1575-1577

Copyright © 2003 by the American Association for the Advancement of Science

Notch-Mediated Restoration of Regenerative Potential to Aged Muscle

Irina M. Conboy,1 Michael J. Conboy,1 Gayle M. Smythe,1 Thomas A. Rando1,2*

Abstract: A hallmark of aging is diminished regenerative potential of tissues, but the mechanism of this decline is unknown. Analysis of injured muscle revealed that, with age, resident precursor cells (satellite cells) had a markedly impaired propensity to proliferate and to produce myoblasts necessary for muscle regeneration. This was due to insufficient up-regulation of the Notch ligand Delta and, thus, diminished activation of Notch in aged, regenerating muscle. Inhibition of Notch impaired regeneration of young muscle, whereas forced activation of Notch restored regenerative potential to old muscle. Thus, Notch signaling is a key determinant of muscle regenerative potential that declines with age.

1 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305-5235, USA.
2 GRECC and Neurology Service, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.

* To whom correspondence should be addressed. E-mail: rando{at}

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