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UNM researchers search for key to longevity

Mark McCormick, an assistant professor in UNM’s department of biochemistry and molecular biology, looks at roundworms in his lab. (Source: Jett Loe/Unm)

“I’ve got one that’s 54 days old!” says Christine Robbins. With a touch of whimsy, she adds, “I think I’m going to name this one Cleopatra.”

Robbins, who manages Mark McCormick’s laboratory in UNM’s Biomedical Research Facility, is talking about an unusual example of Caenorhabditis elegans — a tiny roundworm known as a nematode. The typical nematode lives for only 14 to 21 days.

“Sometimes we name the ones that live the longest,” says McCormick, an assistant professor in the department of biochemistry and molecular biology. “We get kind of attached.”

McCormick’s research focuses on the molecular mechanisms of healthy aging. Surrounded by stacks of petri dishes, his graduate students spend their time staring into microscopes and rapidly entering numbers onto large spreadsheets open on computer screens in front of them. They are measuring how long the nematodes remain active.

Genes, which are like our body’s blueprints, are found in every cell. They can define every aspect of our existence, from building our bones, creating our muscles and maintaining our health to predisposing us to disease and influencing how we age. McCormick’s lab studies the genes that affect the replicative life span in yeast and healthy aging in nematodes by using single genetic “knockout” models.

In these models, one gene at a time is deleted, then the longevity of the offspring is measured. McCormick has collected thousands of these different models. By using these single knockout models and measuring how short or how long these tiny organisms live, he hopes to identify genes that can be targeted with therapies to extend life.

In fact, McCormick has already identified some new ways to extend life span, through multiple biological pathways in yeast and nematodes that are surprisingly similar in humans – hence Robbins’ excitement about Cleopatra’s longevity.

By first understanding this process of extending life in smaller, less complex species, McCormick hopes that his lab can one day translate their work to much more complex organisms, such as mice and human beings. His team uses machine learning, computer coding and complex pathway analyses to assess these large, complex data sets of multiple single genetic knockouts.

Testing in these small critters allows his lab the ability to study life span in a much shorter time frame rather than in more complex animals such as mice, which can live two years, or macaque monkeys, which can live up to 27 years.

McCormick, who came to UNM in 2017, is a mentored principal investigator through UNM’s Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, an international powerhouse of scientists and equipment.

McCormick and his team next hope to explore their findings in mammalian cells to see whether they show the same sorts of genetic changes associated with extended life span.

“We’re reverse-engineering an incredibly complicated machine,” McCormick says. “It’s painstaking, but it’s a very powerful approach.”