How molecular randomness may drive differences in lifespan

“Biological stochasticity”—random events at the molecular and cellular level—might be one of the biggest, most overlooked drivers of differences in how we age, says Ryo Sanabria.

How long you live may be determined not just by one’s genes and lifestyle but also by metaphorical rolls of the dice happening inside the body, according to a new scientific review led by the USC Leonard Davis School of Gerontology.

Published in the journal GeroScience, the study posits that randomness at the molecular and cellular level—what the researchers call “biological stochasticity”—is a key part of why living things age differently, even when everything else is the same.

“Even when scientists control everything—genes, diet, and environment—virtually identical organisms still age very differently,” said corresponding author Ryo Sanabria, assistant professor of gerontology at the USC Leonard Davis School.

“This groundbreaking review introduces the ‘stochastome’—a wild, fascinating concept that puts randomness front and center in the aging process. It’s a thrilling, mind-bending look at how randomness is hardwired into life—and might just be the key to understanding aging in all of us.”

The team studied differences in aging outcomes in tiny worms called Caenorhabditis elegans, or C. elegans. These worms are perfect for this kind of study because they can self-fertilize to reproduce, meaning the offspring will have the same genes as the parent, Sanabria explained.

Scientists can also tightly control environmental factors: what they eat, how much light they get, and even the air temperature. But most importantly, despite the simplicity of the worm model, C. elegans shares features of aging with humans, making many discoveries translatable to humans.

Significant differences under identical conditions

Even with the strict standardization, the worms aged differently from one another; some lived long, healthy lives, while others declined quickly, even though nothing about their genes or environment was different. Most likely, these differences come from random events that happen inside the body; processes such as protein folding, gene expression, and cell behavior can all vary by chance, said Adam Hruby, biology of aging Ph.D. student and first author of the study.

These random changes are part of a bigger system that’s been termed the “stochastome,” a collection of unpredictable biological events that influence how each organism ages.

“What we’ve found from reviewing the literature is that random events can be responsible for differences in biological outcomes at practically all levels of biology,” Hruby said. “These seemingly small differences have a dramatic impact on an organism as it ages, ultimately affecting both health in later life and overall lifespan.”

In one such example, the scientists examined how certain proteins behaved in the worms. In some worms, the proteins folded correctly and kept cells healthy, but in others, they didn’t; the misfolded proteins correlated with faster aging. However, the outcome couldn’t be traced back to specific genes or external causes; it seemed to happen by chance.

The team also explored how random changes during development, such as how brain cells grow or how reproductive cells divide, can set the stage for how someone ages later in life. Even stress responses, like how cells react to heat or infection, showed large differences from one individual to the next, despite being under identical conditions.

These findings help explain why human identical twins, who share the same genes and are largely raised in the same environment, can exhibit differences in aging and lifespan of 15%–20%, Sanabria noted. While lifestyle and environment do matter, they may not tell the whole story.

“This work suggests that biology is secretly chaotic at every level, from twitchy neurons to molecules that fold (or misfold) by chance,” Sanabria said. “These random events might be one of the biggest, most overlooked drivers of how we age.”

The idea of the stochastome could change how scientists approach aging and age-related diseases like Alzheimer’s or Parkinson’s. Instead of just focusing on genes or the environment, researchers might need to study and measure these random processes to better predict or treat age-related decline. If doctors can one day measure someone’s unique biological “randomness,” they may be able to better predict their health risks and design treatments that fit the individual more precisely.

“The stochastome isn’t just a new term; it’s a new frontier,” Sanabria said. “And it’s insanely cool.”