Knocked down a Notch with age

As we age, it seems to be increasingly difficult to recover from injuries. According to research from Irina Conboy, Thomas Rando, and colleagues (Stanford University and the Palo Alto VA Medical Center, Palo Alto, CA), part of the blame for this age-related decline belongs to lazy stem cells that sit idly by rather than repair injuries.

Normally, injuries to muscle tissue activate the stem cell-like satellite cells, which then multiply and differentiate into myoblasts that can fuse with and thus repair injured muscle fibers. The injury-induced proliferation is a function of the Notch pathway. But Rando's group shows that satellite cells in older animals are unable to activate Notch and so do not repair injured muscle.

Notch gets inactivated because aged muscle cells do not up-regulate Delta, the extracellular Notch ligand. In young or adult mice, Delta expression was induced by injury, and satellite cells promoted tissue repair. Repair could be prevented by blocking Notch activation. Wound repair was restored in aged mice by antibody activation of Notch. In the future, a blood-borne nonimmunogenic Delta mimic might enhance muscle regeneration in the elderly.

It is unclear why or how Delta induction fails in older animals. Declining healing powers may be an evolutionary advantage, as some biologists argue that aging, by getting rid of post-reproductive individuals, is beneficial to the population as a whole. ▪

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