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Older people’s immune cells get fuzzier marching orders than those of younger people

Older people are more susceptible to infection, cancer, and autoimmunity than younger people. This may be the result of our immune cells' receiving increasingly random marching orders as we age.

You already knew this: The older we get, the more susceptible we tend to become to infections, cancer, autoimmune disorders — in short, to all the things you don't get when your immune system is acting like a just-off-the-lot Ferrari instead of a rattling, rusty jalopy.

That may be because many older people’s immune cells get a fuzzier set of marching orders than do those of younger people, as I wrote in my news release about a paper published in Cell.

Your fat cells and brain cells (and, I hope, mine, too!) are quite different from one another. Did you ever wonder why that's true? After all, virtually every cell in your body contains essentially the same DNA — the collection of recipes for all the proteins that do the bulk of a cell's work. Yet, skin cells and muscle cells, sick cells and healthy cells, immature versus mature versus senescent (or no-longer reproducing) cells — they're all acting differently despite their common genetic underpinnings (assuming the cells we're talking about are coming from the same person). So what's going on?

Here's the story: The DNA in each of your cells is closely associated with a set of proteins called histones that help pack the DNA tight so a cell nucleus's 23 pairs of chromosomes don't unravel and sprawl like surrealistic spider webs all over the place. Histones also perform another critical function. They help select which of the 22,000 or so genes in each cell are active and which are not being expressed. The current lineup of active and inactive genes determines how the cell as a whole functions.

One way to look at this is to picture a neighborhood in which every house (each house representing a different gene or group of adjacent genes) is surrounded by a big white picket fence that restricts access to it. The picket fences are the histones.

Now imagine two opposing warrior gangs armed with spray paint. The Snoop Gang wants to get inside the houses and "take a look around." It sprays red paint on every fence its members plan to cut holes in so they access the homes.

The OuttaSight Gang, for some reason, wants some houses blocked from view. This gang spray-paints blue graffiti on fences surrounding those buildings. Gang members later lay down a solid wall of bricks around each blue-sprayed fence.

The "red graffiti" sprayed on genes' surrounding histone "fences" (not a great physical approximation, by the way, but a decent heuristic metaphor) beckon like beacons to massive molecular machines that read our genes and initiate construction of the proteins for which each gene is a recipe. The "blue graffiti" steer those gene-reading machines away. (There are other monstrous molecular machines that, analogously to the two opposing gangs I've conjured up above, "paint" histones "red" or "blue".)

The last thing I'll say by way of salvaging my metaphor is that the red and blue paint sprayed on fences are actually two different sets of small chemical adjuncts that get affixed to histones. A fence often simultaneously sports both red and blue paint.

In the Cell study, immunologists PJ Utz, MD, Purvesh Khatri, PhD, and Alex Kuo, PhD, and their colleagues showed that the histones guarding our DNA in immune cells (and very likely in other cells as well) get increasingly graffitied with increasing age — and, like fences in different neighborhoods, some of them a lot more, and a lot more randomly, than others. That may explain why some older people elude the ravages of old age better than others do — their immune systems continue to resemble those of their younger selves rather than go increasingly out of whack with advancing age.

And it may lead to treatments that, by selectively erasing or encouraging particular graffiti on particular fences, can treat disease or slow the aging process.

Photo by Maurits Verbiest

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