A closet full of worms could shed light on the mysteries of aging

Not far from popular Barceloneta Beach in Barcelona, ​​​​Spain, an underground room houses 35 office scanners stored in refrigerated chambers. Nicholas Stroustrup, an American biologist, is the owner of the key to the door of this strange place, pervaded by the roar of a very powerful air conditioner. “That’s the lifetime machine!” he yells so he can be heard over the din. The scientist carefully opens the lid of one of the scanning devices. Inside are hundreds of worms. Hundreds more appear under a different cover. He estimates that there are more than 20,000 worms in the room. The youngest keep moving: they explore their environment restlessly. It is easy to get dizzy looking through the microscope at the elders motionless and wrinkled awaiting death. This unusual machine, Stroustrup claims, could unlock the mysteries of human aging.

The scientist shares a surprising consideration: There’s a lot of randomness in aging that has nothing to do with genetics — a person can die at 60 while their identical twin lives to be 90. His worms, he explains, aren’t that different from humans. They are tiny animals, barely a millimeter long, with a ridiculous and precise number of cells: 959, no more and no less, excluding the ova and sperm. A human being consists of about 30 trillion cells. But despite their tiny size, these worms have everything: a mouth, an anus, a nervous system with 302 neurons, skin, genes, muscles.

The biologist, who compares aging with the game of roulette, tries to unravel its enigmatic rules. Its lifespan engine scans the worms hourly from birth to death. They usually live about 18 days, but scientists run all sorts of experiments to see what happens: they change their diet, stress them, give them drugs, change their genes, expose them to pathogens, raise or lower their temperature. Stroustrup thinks back. He has worked with “millions” of worms and recalls some living for 50 days, which is the equivalent of a human being’s age of 225 years. Why did they live so long while their identical siblings did not? They do not know.

Stroustrup had the idea for the lifespan machine when he was a 22-year-old doctoral student at Harvard University. Lacking the money for fancy automated microscopes, he went to a store and bought an ordinary office scanner. When he first scanned a worm, he was amazed at the resolution. With a meager investment, he was able to study tens of thousands of animals simultaneously.

His first findings were published in the journal Nature in 2016, and the data came as a surprise. More or fewer groups of identical worms lived in each experiment, but there was always a pattern: within the same group, some lived longer than others. There was a constant randomness in the aging process. Stroustrup’s team has now gone further and looked at another factor in addition to longevity: how long the worms maintain their vigorous movement.

The intuitive idea is that both animals and humans have biological ages that may or may not differ from their actual ages. A person may be 70 years old based on their date of birth, but their cells could be closer to 55 years old. Stroustrup’s experiment suggests something else, which is quite different. The worms that sustain vigorous movement for longer — a reflection of healthy living — also live longer. However, statistical differences indicate that they are two independent variables. His study, recently published in the journal PLOS Computational Biology, states that worms have at least two biological ages: one that determines the end of violent movements and another that marks the moment of death. Stroustrup suspects that there is in fact a “constellation” of biological ages depending on which part of the body is seen.

Can a worm’s longevity really reveal the key to human aging? Stroustrup sarcastically responds with another question: “Can human aging research itself unlock the mysteries of human aging?” Repeating his experiments on humans, he argues, would take decades. Even centuries. The current focus is on looking for other variables that are highly correlated with aging, such as the so-called epigenetic clock, chemical marks on DNA used to measure biological age. If a drug given to a human had an effect on this epigenetic clock, one might assume that there would also be an effect on aging, but it would take decades to confirm this. Stroustrup’s new study suggests it’s not that simple. If there are multiple biological ages, one of these indicators may indicate greater youth, while another indicates old age. Many companies are already selling these controversial biological age tests.

The worms Stroustrup uses belong to the species Caenorhabditis elegans, which is already the center of experiments that have won three Nobel prizes: two for medicine (2002 and 2006) and one for chemistry (2008). The first was for Sydney Brenner, the South African biologist who studied the function of DNA in these worms in the 1960s. “Genetics is the master science of biology. In fact, it’s the only science and all others are ways of understanding what genes are doing,” Brenner said in his memoir. In Stroustrup’s laboratory, Indian biotechnologist Natasha Oswal and Spanish neuroscientist Andrea del Carmen inactivate worm genes in the Barcelona basement. Del Carmen points out that other labs have made their worms live ten times longer with a single mutation. “Durability is very malleable,” she points out.

Biochemist Carlos López Otín, an expert on aging at the University of Oviedo, points out that Stroustrup’s new experiment shows “a negative correlation” between the period of vigorous movement of the worms and the length of the period that follows. “In other words, animals with long healthy lives would be doubly lucky if they experienced a shorter period of terminal decline,” he says. López Otín – who did not take part in this study – warns that more research on the molecular mechanisms involved is needed to confirm that the results in worms can be extrapolated to humans.

Italian hematologist Carolina Florian welcomes the new work and emphasizes that aging is a highly complex process. “Not everyone ages at the same rate, and the cells and tissues of our body can even age at different rates,” explains Florian from the Bellvitge Biomedical Research Institute in Hospitalet de Llobregat (Barcelona). “Given the complexity of aging and the difficulty of even defining exactly when a cell, tissue or organism is old, it’s very easy to run into confounders,” she continues. “For that very reason, this study in worms has really important implications for our current understanding of how biomarkers can predict human aging.”

Florian encourages the scientific community to keep going and developing innovative experiments that unveil the true mechanisms of aging. “We are already fully aware that aging is a biological process and that it is possible to treat it to extend lifespan.”