Uncovering the biology of growing old

(Press-News.org) Scientists have long sought measurable signs in the body, called biomarkers, that reliably reveal our biological age or predict future health issues. Now, a new study in dogs—an ideal model for this research because they share our genetic diversity, diseases, and home environments—has uncovered molecular clues that could shed light on how aging unfolds in pets and people alike.

For the study published October 22 in Aging Cell, scientists from the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, University of Washington, and other institutions analyzed blood samples from a group of nearly 800 dogs enrolled in the Dog Aging Project, a long-term, multi-site study of aging in these companion animals. They found that about 40% of the small molecules circulating in dogs’ blood change with age.

“These molecules, known as metabolites, are basically the building blocks of life,” says Daniel Promislow, a senior scientist and scientific advisor at the HNRCA and the study’s senior author. “They serve as the raw materials for forming proteins, DNA, and other cellular components, and play a critical role in keeping cells alive.”

The researchers found that one type of rarely studied metabolite, called post-translationally modified amino acids (ptmAAs), appeared strongly linked with aging across dogs of all breeds, sizes, and sexes. “These metabolites are created in two ways in the body,” explains Promislow. “The bacteria in our guts can make ptmAAs as we digest our food, or they can show up when proteins break down.”

While the source of these ptmAAs is still a mystery, the authors find clear indication that kidney function is critical. Kidneys normally filter the byproducts of protein breakdown out of the blood. And when the team looked closer at markers of kidney function in the dogs’ blood and urine, they found that as kidney function declines, ptmAAs build up—possibly explaining why some dogs age more healthily than others and offering clues for humans, too.

Now that the researchers have compared younger and older dogs to see how their blood chemistry differs at a snapshot in time, the researchers plan to follow changes in metabolites in the same dogs over several years. The scientists will seek to identify gut microbes that might change in abundance with age and influence the ptmAAs. They also are interested in using owner-provided data to determine if changes in muscle mass—a common phenomenon in both aging dogs and people—are linked to these ptmAAs.

By tapping longitudinal data from many different molecular measures, the researchers aim to understand whether these biomarkers truly track the pace of aging and predict future health or longevity—and study if potential anti-aging treatments change these biomarkers. The team also hopes to compare these patterns with how metabolites change in people.

“We have a tremendous opportunity to understand the causes and consequences of aging and to discover ways to ensure that both species enjoy the healthiest aging trajectory possible,” Promislow says.

 

Benjamin R. Harrison from University of Washington’s Department of Laboratory Medicine and Pathology is first author of this study. Research reported in this article was supported by the National Institutes of Health’s National Institute on Aging under award number U19AG057377, and by the Glenn Foundation for Medical Research, the Tiny Foundation Fund at Myriad Canada, the WoodNext Foundation, the Dog Aging Institute, and a cooperative agreement with the U.S. Department of Agriculture's Agricultural Research Service. Complete information on authors, funders, methodology, limitations, and conflicts of interest is available in the published paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. 

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