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Notch-Mediated Restoration of Regenerative Potential to Aged Muscle
Irina M. Conboy,1Michael J. Conboy,1Gayle M. Smythe,1Thomas A. Rando1,2*
A hallmark of aging is diminished regenerative potential oftissues, but the mechanism of this decline is unknown. Analysisof injured muscle revealed that, with age, resident precursorcells (satellite cells) had a markedly impaired propensity toproliferate and to produce myoblasts necessary for muscle regeneration.This was due to insufficient up-regulation of the Notch ligandDelta and, thus, diminished activation of Notch in aged, regeneratingmuscle. Inhibition of Notch impaired regeneration of young muscle,whereas forced activation of Notch restored regenerative potentialto old muscle. Thus, Notch signaling is a key determinant ofmuscle 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}stanford.edu
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