Science helps old mice age gracefully

There was some interesting research out of the Mayo Clinic announced this week. The study focused on a new method to combat aging, though not, significantly, one that could extend life. Instead of living forever, Darren Baker and colleagues would just like to help people enjoy the time they do have—by reducing the physical downsides of aging, such as lost muscle and stiff joints.

Their method centers around something called senescent cells, normal cells that have basically shut down all growth, but continue to release chemicals into the body. Some scientists have suspected this process of cellular senescence contributes to the negative physical effects of aging and Baker's team was able to provide some big support for that theory. They killed senescent cells in the bodies of fast-aging mice. Those mice went on to age more gracefully, delaying the physical breakdown of their bodies. Ed Yong explains:

Baker exploited the fact that many senescent cells rely on a protein called p16-Ink4a. He created a genetic circuit that reacts to the presence of p16-Ink4a by manufacturing an executioner: a protein called caspase-8 that kills its host cell. Caspase-8 is like a pair of scissors – it comes in two halves that only work when they unite. Baker could link the two halves together using a specific drug. By sneaking the drug into a mouse’s food, he activated the executioners, which only killed off the cells that have lots of p16-Ink4a. Only the senescent ones get the chop.

Baker tested out this system in a special strain of genetically engineered mice that age very quickly. It worked. The senescent cells disappeared, and that substantially delayed the onset of muscle loss, cataracts, and fat loss. Typically, around half of these mice show signs of muscle loss by five months of age. Without their senescent cells, only a quarter of them showed the same signs at ten months. Their muscle fibres were larger, and they ran further on treadmills. Even old mice, whose bodies had started to decline, showed improvements.

It really should go without saying that there's a big jump between getting something to work in mice and getting it to work in people. So do not expect your doctor to be able to kill off your senescent cells anytime soon, if ever. There's also potential risks to this therapy and a lot we don't yet know about it. Will this work as well in mice that age at a normal rate? Will killing senescent cells allow us to delay or eliminate other signs of aging, or just muscle loss and cataracts? If you kill of senescent cells, will damaged cells continue to grow, producing cancer?

When you're thinking about a study like this, it's probably best to treat it as an interesting discovery about the way mammal biology might work, rather than something that has any immediate practical medical applications for humans. From that perspective, this is pretty cool science.

Bonus fun: Read Ed Yong's write-up of the study. Then read this version written by a reporter at the New York Times. Then think about how much you would have misunderstood about this study if you'd only read the New York Times story.

Thanks Doug!

Image: The Apple Mouse, a Creative Commons Attribution Share-Alike (2.0) image from moparx's photostream


  1. The thing that naively concerns me the most is the fact that most populations of neurons have also stopped dividing.  It’s likely they operate in a different manner than other cell populations, given their ridiculously high energy usage, but I did notice that there was no cognitive testing in the comparisons here.

    1. In the real write-up, they note that neural cells don’t use the same marker proteins and were exempt from execution. And I suspect that amidst the battery of tests, the rodents suddenly acting brain-dead would have warranted some attention.

  2. I’m engaged in a similar study, except that mine makes extensive use of athletic equipment and computer programming. So far I’m in better condition, physically and cognitively, than I was ten years ago. However, I haven’t yet been able to replicate these results in mice (or my cats, for that matter).

  3. For a while I thought that a cure were invented for the yellowed plastic of my old commodore 64 but then I read the rest of the post.

    (I don’t mean to downplay the research, hopefully they have whole thing figured out before my own casing turns brittle)

  4. Can’t read the article behind its paywall. I really wish Nature would switch to a PLoS-like charge-the-author model instead of charging the world $30 to read a damn article. Err. Anyway – is there any discussion there of the effects of this treatment on normal mice relative to untreated mice? Also, it should be noted that these mice have the genetic circuit engineered into them – you can’t just pop some pills and kill off your problematic senescent cells this way.

  5. See also Senesco Technologies, which has been using senescence for food treatment for a while and is in the middle of long-term testing of controlling senescence for cancer treatment, with the potential of chemotherapy that is more effective but doesn’t make people sick.

    Disclaimer, I own 3000 shares, which sounds like a lot, but really isn’t. I bought it because I love the idea of not watching people I love suffer through chemo ever again.

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