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Can You Unwrinkle A Raisin?

The questions that kids ask about science aren’t always easy to answer. Sometimes, their little brains can lead to big places that adults forget to explore. That is what inspired our series Science Question From A Toddler, which uses kids’ curiosity as a jumping-off point to investigate the scientific wonders that adults don’t even think to ask about. The answers are for adults, but they wouldn’t be possible without the wonder that only a child can bring. I want the toddlers in your life to be a part of it! Send me their science questions, and they may serve as the inspiration for a column. And now, our “toddler” …

Can you turn raisins back into grapes? — Kara H., age 7.

They probably don’t cover Prohibition in first-grade U.S. history, so Kara can be forgiven for not being well-informed on the fine, American tradition of clandestine home booze manufacturing. If she had been, she’d already know the answer to her own question. (*Stares pointedly at the American educational system.*)

Short version is this: Back when you couldn’t just go buy a bottle of wine, folks would, instead, buy a giant brick of raisins, soak them in water to rehydrate the dried-out fruit and then store that juice in a dark cupboard for 60 days.

This is how the alcohol-drinking public pulled itself up by its bootstraps. The important takeaway is that you can make shriveled raisins plump again — but that’s not the same thing as turning them back into grapes. The process of making a raisin changes the fruit at a molecular level. It increases the concentration of sugars (important to that whole home wine-making operation). It alters the nutritional value. It even changes the tissue of the fruit, so that rehydrating a raisin is less like making it young again and more like turning it into a leaky water balloon. So, you can’t really turn a raisin back into a grape even when you give it its fluids back.

But the joy of Science Question From A Toddler is that we don’t end with squashy old fruit (nor do we stop at the kid’s question). Thinking about rehydrated raisins got me thinking about the way all of us, every second, are also on an irreversible journey of cellular change. Age may be nothing but a number (we’ve been trying to convince pedantic readers of that since we named a column “Science Question From A Toddler” and went on to feature questions from kids as old as 7). Aging, on the other hand, is more complicated — an ongoing process in which our very cells stab us in the back with the second law of thermodynamics. (Et tu, physics?) Neither raisins nor cellular aging can be reversed. But, increasingly, scientists are convinced that aging, at least, could be changed and slowed down in ways that might feel every bit as magical as a bottle of illegal basement raisin wine.

First off, cells change as they age. Literally, the shape and appearance of the human cell change over time, said Denis Wirtz, professor of chemical engineering at Johns Hopkins University. Both the cell itself and the nucleus that carries its genetic material become larger with age and more undulated, Wirtz said. “Like a wavy contour as opposed to a rounder, smooth contour,” he told me. “It starts folding into weird shapes.” An old cell looks, if you will, a bit more like a rehydrated raisin than a fresh grape.

One way that ends up being important is that it enables scientists to guess your age with remarkable precision, within two and a half years, just by looking at 20-30 cells from the inside of your cheek, Wirtz said. That’s because both the average size and shape and the distribution of sizes and shapes change. With just a small sample, experts can see that older people not only have bigger, more wrinkly cells, but they also have greater variation in the sizes and shapes of individual cells.

While Wirtz’s team has looked for variations that showed how humans changed as they aged, a team that includes Matt Kaeberlein, director of the Healthy Aging and Longevity Research Institute at the University of Washington, has been looking for how cellular aging looks across a vast number of species — from yeast to dogs. Turns out, there are a lot of mechanisms of aging that all these diverse creatures have in common. One example is a thing called the target of rapamycin (TOR) signaling pathway, a protein in the cell that helps it figure out what nutrients are available in the surrounding environment and make a “decision” about whether it’s time to grow or time to slow down and sit tight. When the TOR pathway is less active — that is, when it senses an environment with less available food — it ends up setting off a chain reaction that not only slows cell activity but also slows aging.

If that sounds familiar, Kaeberlein said, it’s probably because the TOR pathway is the mechanism behind all those “fasting mice live longer” studies — and the backyard-biology food-restriction diets that some biohackers hope will grant humans the same results.

These shared aging mechanisms are interwoven, working together and affecting the way one another plays out, Kaeberlein said. Take senescence, another cross-species aging factor, which turns out to be linked to TOR in interesting ways.

Senescence is basically when old cells act all weird. Senescent cells stop dividing. They stop functioning normally. And they don’t just stop doing their jobs — they ruin the whole neighborhood. Senescent cells secrete chemicals that increase inflammation all over the body, Kaeberlein said. That’s a big problem because inflammation is associated with a whole host of health problems, including coronary heart disease, diabetes and cancer. And the stuff that senescent cells are spewing can also increase your likelihood of cancer, Wirtz said. If you take precancerous cells and expose them to the secretions of senescent cells, he said, they suddenly tip over the edge from “a little bit eccentric” to “homicidal.” “It’s really spooky,” he told me. “[Senescent cells] are not causing cancer, but they are making sure to push those cells tempted to become cancerous to actually do it.”

Scientists don’t understand everything there is to know about senescence or the stuff that senescent cells excrete. But one thing they have figured out: There’s some connection to TOR pathways. Fasting isn’t the only way to get that TOR-related slowing of the aging process. There are also drugs that seem to flip the same switches, Kaeberlein said. And those drugs seem to reduce the impacts of senescence. It’s an amazing shift, associated with a restoration of physical, cardiovascular and cognitive function.

It’s also a change that is associated with visible shifts in the appearance of the cells, Wirtz said. They get smaller again. They become more round. They start to look less like bloated, wrinkly rehydrated raisins — and more like grapes.

It’s not exactly turning back the hands of time, experts cautioned. But it is truly amazing stuff. “If you’d asked me 10 years ago, I’d have said it would be very unlikely to reverse the effects of aging,” Kaeberlein said. “What we’ve learned over the last decade is that it’s turned out to be much easier to restore lost function.” At least, he added, in mice. People are the next frontier. Grapes, maybe not so much.

Maggie Koerth was a senior reporter for FiveThirtyEight.

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