Diet or Drugs, Calories or Carbohydrates? Longevity medicine comes for your dog.
Beneath the headlines, the carbohydrate-insulin model is now hiding in plain sight.
Let’s talk about Chilly, the endearingly cute animal posing heroically on our front stoop in the photo below.
We adopted Chilly on May 5th, 2018. He’s a mutt, one of those dogs that looks like he was assembled from leftover parts of different breeds. If he does have a breed of his own, it would be Korean village dog. We adopted him from an agency that collects strays in Korea and transports them locally for adoption. Within roughly seconds of meeting him, he had won my wife, Sloane’s, heart. Now Chilly is nine, and if you were to ask Sloane what she would do to prolong his life — as I just did — she would say “anything.”
This would seemingly include putting Chilly on a “new pill [that] could soon extend dogs’ lives,” as the sub-head of an article in The Atlantic suggested earlier this month. The headline, though, included a caveat: it said only that our “next dog may live longer,” implying the pill might come too late for Chilly. We can only hope.
But the story raises a few other questions. They’re ones we’re more used to asking — along the lines of: diet or drugs? If a drug extends life by mimicking the effects of a restricted diet, which this one appears to do, why not consider diet the more optimal strategy?
The Atlantic story is also an example of how once-revolutionary notions about diet, health, and disease have become sufficiently mainstream that the writers of these articles seem unaware they were once considered radical. The ideas are still hopelessly entangled with conventional thinking, but progress is being made. The New York Times had another one, and we’ll discuss that, as well. The ideas, of course, concern the roles of carbohydrates and insulin in health and disease. What was once quackery is now discussed without a second thought. The paradigm is shifting, although the entanglement with conventional thinking still makes me wonder how far it will go.
A longevity pill for dogs? Could you turn it down? Or maybe do better?
Let’s start with our dog longevity story. The writer, Ross Andersen, has been writing about science for the Atlantic for well over a decade, but little of it was previously relevant to diet. He’s one of those writers who seems capable of writing thoughtfully on a different scientific subject weekly, which is not easy. That kind of weekly production, though, requires that the articles be based on a relatively small number of interviews (if any). If there’s a deeper story—a long-simmering scientific controversy, for instance—a writer like Andersen can easily miss it.
The gist of Andersen’s article is that the FDA is on the verge of approving a longevity drug for dogs. The company that makes it is called Loyal, founded in 2019 by a young researcher named Celine Halioua. Why dog longevity instead of humans? Well, one reason is that Halioua grew up in a household full of animals. Another is that dogs don’t live as long as humans, so establishing that a drug actually works—makes them live longer—shouldn’t be quite so difficult to do. And then, as Andersen says, “[f]ederal approval for animal drugs is easier to come by than it is for human drugs.”
That scientists could extend the lives of any species, occasionally dramatically, had been demonstrated decades ago, Andersen writes, but “mostly on… tiny animals that people don’t care much about.”
By the early 1990s, a molecular biologist named Cynthia Kenyon had for years been arguing that aging is not simply a matter of accumulated wear and tear. To Kenyon, who now serves as the vice president of aging research at Calico, the fact that animals have such a wide range of lifespans was evidence that the aging process is directed by genes.
In 1993, Kenyon doubled the lifespan of a roundworm, Caenorhabditis elegans, with the tweak of a single gene that targeted its insulin receptors. Scientists have since used similar genetic tricks to substantially extend the lives of flies. Most tantalizing, they have done it in adult mice.
That it targeted a gene related to insulin was why I discussed Kenyon’s work in my 2007 book Good Calories, Bad Calories. Specifically, it was the single worm-equivalent of a trio of insulin-related genes in humans, which includes both insulin and insulin-like growth factor. This kind of research assumes the evolutionary argument that genetic mechanisms are conserved from simple organisms to humans, and it suggests the hypothesis that elevating circulating insulin and IGF levels will increase disease risk and shorten lifespan.
What Andersen did not discuss in his article, but I did in Good Calories, Bad Calories was what Kenyon did next in her research. Here’s GCBC:
Once it became clear that the mutations that prolonged longevity in worms were those that reduced the level of activity in the worms’ insulin/IGF pathway, Kenyon began a series of experiments based on a single question: What would happen if she fed worms glucose, in addition to their preferred diet of bacteria? Kenyon added 2 percent glucose to the bacterial medium in which the worms lived, and the lifespan of the worms was reduced by a quarter. Kenyon is still working to establish the nature of this adverse effect of glucose. Her hypothesis: Just as mutations increase lifespan in worms by decreasing activity in their insulin/IGF pathway, glucose shortens the lifespan of worms by increasing activity in the same pathway. In October 2004, when Kenyon presented the results of these experiments at a Cold Spring Harbor conference on the “Molecular Genetics of Aging,” she concluded her presentation with a simple, albeit radical question: “Could a low-carb (i.e., low glycemic index) diet lengthen lifespan in humans?”
That tells us where we’re going in this post, but Andersen didn’t in his story. If a diet that stimulated insulin secretion shortened the lifespan of experimental animals, maybe a diet that didn’t would not. What appears to be a benefit for longevity may actually be the reduction in the dietary component that shortens lifespan. Kenyon saw the implications immediately.
