Retrospectacle: A Neuroscience Blog

Darling of Nature and current researcher at UM, Dr. Sean Morrison, has recently authored a paper implicating a protein called ‘inhibitor of cyclin-dependent kinase 4A’ in the decline of a stem cell’s lifespan.

A single molecular switch plays a central role in inducing stem cells in the brain, pancreas, and blood to lose function as they age, researchers have found. Mice lacking that switch show considerably reduced aging-related decline in stem cell function and tissue regeneration.

“People tend to think that old tissues have less regenerative capacity because they are wearing out,” said Sean J. Morrison, a Howard Hughes Medical Institute investigator at the University of Michigan who led the study of the switch’s role in the brain. “This work shows that they are not just wearing out; they are actively shutting themselves down.”

The gene which encodes the inhibitor protein becomes increasingly more active as tissues age, providing one clue as to why older tissues have less stem cell activity and take longer to heal. Specifically, Morrison found that in the mouce brain, as this gene’s activity increased with age, in an inverse relationship with stem cell number as well as neurogenesis. Furthermore, knockout mice which lacked the inhibitor gene had enhanced stem cell function and neuronal production, but a difference (as compared to normal controls) was observed only in older mice.

“We didn’t turn an old brain into a young brain by deleting p16INK4a, but the deficient mice did show significantly increased progenitor cell function and neurogenesis with age, compared to normal mice,” said Morrison. “This tells us that p16INK4a is not the whole story, although it’s an important part, and that other genes also regulate the aging process.”

(Hat tip Bob Abu.)


  1. #1 JaysonB
    September 7, 2006



    We need better names for genes, like, “My body may be 80 but my dirty mind is 20,” or shit like that.

    Make em interesting, and collectible like garbage pail kids, and people will come running.

  2. #2 greensmile
    September 7, 2006

    So who can tell me what signals this gene pays attention to? Bora has a lot of knowledge about clocks that can count hours but here we have a clock that should be counting years or perhaps cummulative carcinogen exposure?

    NYTimes took a stab at this story too:

  3. #3 Shelley Batts
    September 7, 2006

    Sounds like an interesting target for siRNA therapeutic knockdown….if that kind of therapy ever makes it into human clinical trials.

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