How to Outlive your ancient genes

The weird role of evolution in popular conversations about health

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I recently picked up Outlive, a new book by Bill Gifford and celebrity physician Peter Attia, MD which promises the middle-aged a roadmap to navigate the second half of life in better health by delaying or avoiding the onset of cancer, cardiovascular, neurologic, and metabolic diseases.

Midway through, and convinced I need to get more exercise, I’m enjoying much of its optimistic if slightly promotional vision of a future oriented toward earlier prevention and more personalization of medicine.

One part of the book that works less well for me is its evolutionary explanation for today’s chronic diseases.

The gist of it is that the responsible dysfunctions in human physiology are the result of beneficial adaptations that occurred hundreds of thousands of years ago during our evolution.

The argument goes something like this. As Homo sapiens are evolving from our hominid ancestors they try to leave Africa but find that they don’t have what’s required to survive in temperate climates. So they go back to Africa, wait around for a mutation(s) that enables fat storage and the selection required for this to spread, and then reemerge with new metabolic machinery that allows them to survive winter and populate the globe.

[M]illions of years ago, our primate ancestors migrated north from Africa into what is now Europe. Back then, Europe was lush and semitropical, but as the climate slowly cooled, the forest changed. Deciduous trees and open meadows replaced the tropical forest, and the fruit trees on which the apes depended for food began to disappear, especially the fig trees, a staple of their diets. Even worse, the apes now had to endure a new and uncomfortably cold season, which we know as “winter.” In order to survive, these apes now needed to be able to store some of the calories they did eat as fat. But storing fat did not come naturally to them because they had evolved in Africa, where food was always available. Thus, their metabolism did not prioritize fat storage….

These same ape species, or their evolutionary successors, migrated back down into Africa, where over time they evolved into hominids and then Homo sapiens—while also passing their uricase-silencing mutation down to us humans. This, in turn, helped enable humans to spread far and wide across the globe, because we could store energy to help us survive cold weather and seasons without abundant food.

There is a lot going on in these paragraphs! But the argument that follows, and runs through Outlive, is pretty simple: these ancient genes are still with us and are really unprepared for Costco. Facing a time of unprecedented caloric and nutritional abundance, they’re driving the metabolic dysfunction behind a variety of human chronic diseases.

“Evolution is no longer our friend, because our environment has changed much faster than our genome ever could. Evolution wants us to get fat when nutrients are abundant: the more energy we could store, in our ancestral past, the greater our chances of survival and successful reproduction….We needed to be able to endure periods of time without much food, and natural selection obliged, endowing us with genes that helped us conserve and store energy in the form of fat. That enabled our distant ancestors to survive periods of famine, cold climates, and physiologic stressors such as illness and pregnancy. But these genes have proved less advantageous in our present environment, where many people in the developed world have access to almost unlimited calories.”

To be fair, the same narrative is popping up everywhere in the popular press. In a recent issue of The Economist, writing about the introduction of the GLP-1 receptor agonists, the magazine twice pins our obesity problem on these same ancient genes:

The reason almost certainly lies in the evolutionary past. In a state of nature food is rarely plentiful, so Homo sapiens has evolved to hang on to fat. (Link)

…

The world’s expanding waistlines are not a sign of the moral failure of the billions who are overweight, but the result of biology. The genes that were vital to helping humans survive winters and famine still help the body cling on to its weight today. The superabundance of hard-to-resist processed foods in recent decades has brought greater convenience and lower costs, but also triggered overeating just as lifestyles became more sedentary. Once the fat is on, the body fights any attempt to diet away more than a little of its total weight. (Link)

Why it’s awkward

Intuitive, big and distant, the explanation sets itself off from skepticism. But the evolutionary narrative needs some scrutinizing, not least because in a weird twist, it ends up being used to pin responsibility for a longer, healthier life on individuals.

First, for a story about human evolution, it assigns too much agency to mutations, as though they were purposefully acting to improve the health of humans. As far as I know, humans are the only primate to deposit fat — so something happened — but that does not mean it was positive change with a purpose. Bill Bryson has a good paragraph in A Short History of Nearly Everything that reminds us not to assume that evolution is necessarily proceeding towards progress or improvement.

Even when DNA includes instructions for making genes—when it codes for them, as scientists put it—it is not necessarily with the smooth functioning of the organism in mind. One of the commonest genes we have is for a protein called reverse transcriptase, which has no known beneficial function in human beings at all. The one thing it does do is make it possible for retroviruses, such as the AIDS virus, to slip unnoticed into the human system. In other words, our bodies devote considerable energies to producing a protein that does nothing that is beneficial and sometimes clobbers us. Our bodies have no choice but to do so because the genes order it. We are vessels for their whims.

Bryson goes on to highlight that natural selection generally weeds out disruptive genes long before they can become permanently troublesome to a species or population. However, the story of our ancient fat-storage genes doesn’t really allow for the possibility of selective pressure at subsequent points after they appear in humans. Instead, after emerging and allowing us to survive and prosper, these genes lurk latent until their negative effects are invoked by the singular caloric abundance of modern times.

In between, you need to believe that the parts of the human genome responsible for diet, nutrition and fat-storage / metabolism didn’t really change for hundreds of thousands of years. It’s tough to think we understand and can confidently summarize the selective pressures on the entire history of human populations, or assume the fat-storing genes emerged independently and stayed that way. No one’s talking about how the genes — again, which ones those are we don’t really know — might have been tied up with other phenomena, genetic or otherwise. Somehow the fat storage machinery stays unaffected by the emergence and evolution of language and culture and farming and so on. It’s all just too orderly and improbable, when it would be simpler and more probable to imagine the fat storage genes were mixed up with all kind of influences along the way. Maybe we evolved a system for defending ourselves against parasites that has the side effect of storing fat, for example. Who knows?

The popular evolutionary narratives also rely on an idea of human life during vast periods of prehistory and history as one long struggle on the precipice of survival. Recent accounts, such as The Dawn of Everything, by anthropologists David Graeber and David Wengrow, dispute such bleak characterizations. Their review of the historical and archaeological evidence suggests the scarcity and struggle we associate with these eras may often be mythical. On top of that, the history of human social organizations is a lot more chaotic and less teleological. The hundreds of thousand of years that have passed since humans evolved have not been a linear progression from prototypical hunter-gatherer to calorie-rich modern civilizations.

How time is disjointed and narratively compressed into scenes in the explanation is one of its more jarring characteristics. We zoom way back to our beginnings as a species to contemplate a diorama of stressful hunter-gatherer life. Then, in the next sentence, we skip many thousands of years forward to a similarly shallow, homogenous modern world, where what were once life-saving mutations suddenly become maladaptive in a novel environment.

Evolution turns up only at convenient moments. It’s onstage in the beginning when our species faces selective pressure early in our emergence and diffusion. Then it all but disappears. How did the biology support or undermine the success of humans during the advent and spread of agriculture, or the development of complex civilizations? It’s hard to imagine these adaptations arose and then had zero interaction throughout the entire accumulated record of the complex and varied lifestyles, diets, environments, and stresses of all the innumerable societies in history, with no proximal effects on survival, reproduction and health.

In short, you have to believe both that the responsible genes are relics and that they’re suddenly active in the modern environment.

Changing how we exercise, what we eat, and how we sleep (see Part III) can completely turn the tables in our favor. The bad news is that these things require effort to escape the default modern environment that has conspired against our ancient (and formerly helpful) fat-storing genes, by overfeeding, undermoving, and undersleeping us all.

You never hear that the genes we share with fruits and vegetables may have implications for our well-being today, even though biochemically we are quite close! As Bill Bryson put it:

Every living thing is an elaboration on a single original plan. As humans we are mere increments—each of us a musty archive of adjustments, adaptations, modifications, and providential tinkerings stretching back 3.8 billion years. Remarkably, we are even quite closely related to fruit and vegetables. About half the chemical functions that take place in a banana are fundamentally the same as the chemical functions that take place in you.

So what?

The whole thing feels like an odd spin on traditional epidemiology. Typically, in many of our chronic disease epidemics, such as asthma, the research suggests the increase in prevalence has occurred so fast and in so many (if not all) of the populations in which it’s been measured that it cannot be explained by genetics. Instead, epidemiologists point to a loss of protective factors and/or an increase in aggressive exposures in the environment. In the case of asthma, these conclusions motivate us to improve air quality and otherwise invest in public health measures to shift the population distribution of risk, not just the odds of an individual getting sick.

In the Outlive argument, the environment has changed quickly, but it’s our sluggish genetics that put us at risk. And somehow that means it’s on you and your behavior to sort it out. There’s not much opening for public health interventions. Instead, it’s an individual clinical prescription: how much you exercise and what kind of exercise you do, how much you sleep and eat, and so on, all of which is informed by a list of underused (and often unreimbursed) biomarker studies that your doctor may or may not be able to interpret.

Outlive draws a line between the evolutionary backdrop and a theory of chronic disease and how we treat it today. The book frames its focus on the four major diseases as the result of an accumulation of insults in individuals over time. “Chronic diseases work in a similar fashion, building over years and decades—and once they become entrenched, it’s hard to make them go away.” Some diseases (appear to) work this way — at least in part. But that perspective misses a lot of important variability. For example, there are plenty of chronic diseases that often emerge in childhood, such as asthma or type 1 diabetes. 

Plenty of other theories about chronic disease don’t locate everything so squarely at the feet of a medicalized consumer. For example, the Barker Hypothesis, also known as the fetal origins of adult disease or the developmental origins of health and disease, links early life nutrition and growth to the risk of chronic diseases later in life. It was first proposed by David Barker, a British epidemiologist, in the late 1980s and early 1990s, based on his observations of historical cohort studies and events, such as the Dutch Hunger Winter. These populations showed an inverse association between birth weight and the incidence of hypertension and coronary heart disease in middle age. The hypothesis gained attention and support from many researchers who found similar associations between low birth weight or intrauterine growth restriction and various metabolic and cardiovascular disorders in different populations and settings. 

The Barker Hypothesis stimulated interest in the possible mechanisms – genetic, epigenetic, hormonal, metabolic, and environmental — underlying these associations. But its popularity has waned in recent years. The criticism: Too much diversity and complexity in individual pathways and etiologies, too little control of important confounders, and a lack of direct experimental evidence. The same weaknesses we’d find in the ancient genes story if we took it academically.

Either way, we’re back then “in our modern world, where this fat-storage mechanism has outlived its usefulness.” Outlive ties us to some primordial past and Barker to our early life in utero, neither of which I can find any practical ways of dealing with today. We could really use some new, evolutionarily-sound ideas to help us think about and act in ways that promote healthful longevity not just as individuals, but more broadly in communities and populations.