Deconstructing Aging in Pursuit of a Unified Theory of Health

Alan Cohen was 18 when he decided he wasn’t sufficiently stimulated by a typical university education and decamped to Japan. There for two years he studied Aikido and taught English, then returned to the U.S. to complete his schooling. An associate professor in Columbia Mailman School Department of Environmental Health Sciences and a researcher in the Robert N. Butler Columbia Aging Center since 2022, Cohen credits the hiatus—during which he began his study of the Japanese language—as an intellectually formative experience. “You can’t speak Japanese well unless you learn to think in a different way,” he explains. Consider, for example, how English speakers think about rodents, with separate words for rats and mice. In Japanese, by contrast, a single word, nezumi, applies to both. Says Cohen: “That experience very early on of learning how different people’s perspectives could be, that’s been a crucial aspect of my development.”

As a scholar of aging, Cohen uses statistical tools to analyze networks of biomarkers for clues to how our bodies maintain homeostasis in response to changing environmental conditions and what happens to those processes as we age. “Most biomedical research tends to look at one cell, one molecule, intervene in one pathway,” he says. “But all of the molecules and cells in our bodies interact—when you intervene on molecule A, it not only affects B and C, but C also affects A again. That idea that our bodies are complex systems is at the core of my research.” Cohen has written extensively on physiological dysregulation, frailty, and other predictors of mortality. A 2022 study published in BMC Biology exploring the health effects of holistic dietary patterns yielded an interactive tool for researchers to test how dynamics among micronutrients affect such outcomes as kidney function or immune system regulation.

In addition to your native English and Japanese, you also speak French and Spanish fluently, have a command of written and conversational Italian, and understand basic Chinese and Korean. How does being a linguaphile affect your scholarship on aging?

My experience of languages—how a concept in one framework doesn’t even exist in another— has led to a deep questioning of fundamental assumptions in the field. In Japanese, there are separate words for hot water and unheated water—an automatic distinction. From a scientific perspective, is there a biological phenomenon of aging? At this point, my research supports the idea that it’s a grab bag of many different phenomena. Using the same word to describe them all misleads the science. There’s also a cultural perspective. In our society, older adults are not valued. That’s led to an assumption that aging is bad, the youthful state is good; that implies that every process that happens with age is a bad thing. But some processes might be neutral or compensating for another process.

You earned a PhD in ornithology. What does that have to do with aging?

My curiosity with aging began in Biology 101, when I learned that plants have specific hormones that they use to kill themselves. I started wondering: Why have a specific system that does that? Why does anything age? Why do some organisms die sooner than others? I studied the physiology of wild birds because my hypothesis was that, compared across bird species, antioxidants would prevent aging.

Did your fieldwork confirm your hypothesis that antioxidants prevent aging?

Most people in ecology and evolution focus on one species. When you do that, you find that say, in this species, this antioxidant does this. But my study had hundreds of species. I didn’t have as much depth in any one species and there wasn’t one picture that made sense. It made me confront the limits of our hypotheses in the field. I got into ecology and evolution because I wanted to be outside spending time in the woods with critters. By the time I finished my PhD, I realized that most researchers in all fields are in front of a computer anyway, so maybe I should go do something professionally in public health—that’s why I did a post-doc in epidemiology and the public health of aging.

How does your ecological training inform your current research?

Ecologists and evolutionary biologists always start with the why questions: why would natural selection have generated a certain pattern or trait? I’m always approaching every question in biology from the perspective of why: Why is this gene doing things this way? What’s the advantage and what’s the cost? Also, ecosystems tend to maintain themselves in balance. This has informed the idea that our bodies are complex systems, which is at the core of my research. Can we understand aging as the breakdown of how a complex system maintains dynamic equilibrium?

What data would you collect if price were no object?

I’d be trying to gather a ton of data on internal dynamics—not just a snapshot in time, but essentially a video at very high resolution of what’s going on with individual molecules, genes, DNA methylation, RNA, so we can learn how the whole system maintains itself in balance. I’m imagining how we can use measures of dynamic equilibrium as markers of health, instead of playing whack-a-mole with specific symptoms. Then we could focus on health across dimensions and diseases by focusing on maintaining or restoring equilibrium.