The bigmouth buffalo, an extremely long-lived species of fish, shows no clear signs of senescence, an accomplishment that may offer insights into the physiological processes that underlie aging.

Scientists found that older bigmouth buffalo in fact seemed less stressed and had better immunity than younger fish. Additionally, the elderly fish weren't more likely than their young peers to have telltale markers of stress and aging seen in the DNA of other organisms. The researchers published the results April 27 in Scientific Reports.

"This idea that there might be organisms that are actually outside the realm of aging in the way that we understand it is still debated," said Derek Sauer, a Ph.D. student in marine science at the University of Auckland in New Zealand and first author of the paper.

However, some animals are known to age very slowly, including naked mole-rats and many cold-blooded, or ectothermic, animals. Understanding how this process varies among different kinds of animals could aid in understanding of vertebrate aging more generally.

"It's really interesting to look at these species that live longer than most humans and continue to reproduce" late in life, Sauer said. "Who's to say some of the things we might find in rockfish or bigmouth buffalo or long-lived sea turtles might not be applicable outside of ectotherms?"

Fish have particularly impressive lifespans; several years ago scientists identified a Greenland shark with an estimated age between 272 and 512 years. In 2019, Sauer's colleagues reported that the bigmouth buffalo can live for at least 112 years, making it the oldest age-validated freshwater fish. These fish are widespread in the United States and parts of Canada, but their northern populations are on the decline and very little is known about them, Sauer says.

For the new study, the team examined several physiological aspects of aging in the long-lived fish. They collected 240 bigmouth buffalo that ranged from 2 to 102 years in age from two river basins in Minnesota and determined the fish's ages using otoliths — calcium carbonate structures that have annual growth rings and are located in the inner ears of fish — and bomb radiocarbon dating.  

To assess how well an individual fish's immune response could fend off pathogens, the researchers exposed samples of blood plasma from the bigmouth buffalo to E. coli and counted how many of the bacterial colonies were killed. The team observed that plasma from older fish killed a larger percentage of the bacteria than plasma from younger fish did.

The researchers determined how much long-term stress the fish had experienced by comparing the relative amounts of two kinds of white blood cells known as neutrophils and lymphocytes. When stress hormones increase, the ratio of neutrophils to lymphocytes also increases. Some of the lowest ratios of neutrophils to lymphocytes were seen in octogenarian and nonagenarian fish, Sauer says. 

"We were really intrigued to see that the oldest fish actually seemed to be experiencing less stress and/or regulating stress more efficiently," he said.

Sauer and his colleagues also examined the animals' telomeres, caps of non-coding DNA that protect the chromosomes from damage. Research in other animals, particularly birds and mammals, indicates that telomeres shorten due to age and stress. However, Sauer and his team found no connection between the age of a fish and the length of its telomeres.

Part of the reason the fish are able to survive for so long may be related to an enzyme called telomerase that helps restore telomere length. In most human tissues, telomerase is only present in low levels. But some fish display high levels of telomerase over their entire lives, Sauer says. 

He and his colleagues only measured telomere length in red blood cells. The next steps to understanding how bigmouth buffalo stave off aging will be to assess telomere length and telomerase concentrations in multiple types of tissues from fish of different ages, Sauer says.

It's possible that bigmouth buffalo have even longer lifespans than scientists have yet realized, he notes, and the physiological processes the researchers examined do eventually deteriorate.

"One explanation for why the oldest fish might appear to be operating in their prime is because they could still very well be in their prime," Sauer said.

Holding senescence at bay likely gives the fish more opportunities to pass their genes on. Sauer and his colleague suspect that bigmouth buffalo need very specific conditions to spawn.

"You want to remain in a prime state because you never know when you're going to have a good year," Sauer said. "You have these really big and fecund individuals that are just remaining ready ... even in really old age, because they might get one good season, and however long they have been waiting for that season, the whole thing can pay off in one go."

One caveat to the new findings is that the researchers weren't able to track immunity, stress and telomere length within the fish over time. However, Sauer says, the amount of variation in these traits didn't diminish with age. This suggests that the elderly fish weren't merely ones that survived because they had superior immune systems or stress management abilities to begin with. 

"It's maybe a little early to take these results and try to apply them to 'fountain of youth' ideas," Sauer said. "But at the same time, we're looking at some of the earliest vertebrates and we're studying the same physiological processes in them that happen in humans."

"It's interesting to see patterns so much different from the way we understand these processes in warm-blooded animals."

The study, "No evidence of physiological declines with age in an extremely long-lived fish," published April 27 in Scientific Reports, was authored by Derek J. Sauer, University of Auckland; Britt J. Heidinger and Jeffrey D. Kittilson, North Dakota State University; and Alec R. Lackmann and Mark E. Clark, University of Minnesota Duluth.