North American freshwater fish called Bigmouth buffalo can live over a century.

– Older bigmouth buffalo have improved immune function compared to younger fish.

There is no link between biological aging markers and chronological age in bigmouth buffalo.

What would it be like to get older without aging? That’s where long-lived bony fish like the bigmouth buffalo — a large freshwater fish native to North America — come in, because they can readily be aged and exhibit some of the longest lifespans among vertebrates, living beyond 110 years.

A small team of researchers from the University of Auckland, North Dakota State University, and the University of Minnesota Duluth found that, in contrast to terrestrial vertebrates, a fish called the bigmouth buffalo showed no evidence of age-related physiological deterioration, even those approaching 100 years of age. Contrary to expectation, the study found that older fish appeared to be less stressed and had greater immunity than younger fish, suggesting age-related improvements rather than declines.

This research paves the way for future research on other extremely long-lived organisms on the mechanisms that underlie variation in the pace of senescence, which could have major implications for our understanding and control of biological aging.

Living things don’t all age at the same rate

There is considerable variation in the rate of aging among living creatures. Some animals have extremely slow rates of aging. For example, captive naked mole rats display minimal changes in physiology or morphology while living more than 28 years, approximately 9 times longer than mice of similar size, and females show no decline in fertility even near the end of their lifespan. In addition, some turtle species display no sign of increased mortality or loss of vigor in old age and older females lay more eggs and have more consistent reproduction than younger females. 

Senescence rates vary from creature to creature

Senescence is a hot term in aging. It’s when cells permanently stop replicating. When this happens, age-related changes begin to adversely affect our body’s ability to function. Although evidence for senescence in aging is accumulating, the pace of senescence varies among and within species. Some species that exhibit extremely slow senescence reveal the notable variation that exists in the pace of senescence and highlights the value of studying senescence in slow-aging species.

Studies on senescence often focus on age-related changes in mortality and fecundity (a term we use for fertility). But they don’t quite get a handle on the changes in the function of physiological systems. For this reason, the physiological systems that contribute to differences in senescence patterns are not well understood, especially in long-lived vertebrates.

Bigmouth buffalo don’t fall apart with age

Here, Sauer and colleagues examined the potential effects of age on multiple physiological systems expected to be involved in senescence in bigmouth buffalo. They investigated the relationship between age and multiple physiological systems that are expected to be important mechanisms of senescence including an aspect of the stress response called the neutrophil to lymphocyte ratio (NLR), immune function, and the lengths of telomeres — the protective end caps to chromosomes that appear to shorten with aging in humans and many animals.

The neutrophil to lymphocyte ratio often increases with age, possibly because the ability to cope with stressors becomes dysregulated. However, Sauer and colleagues found that older bigmouth buffalo had lower rather than higher NLRs than younger ones, suggesting that older fish experience lower levels of chronic stress and may have a more efficient stress response and even greater fitness than their younger counterparts. Also, their findings in bigmouth buffalo indicate that senescence of the immune system is not observed in bigmouth buffalo greater than 90 years old, as bacterial killing capacity — the rate at which the fish kill off bacteria — actually increased with age.

(Sauer et al., 2021 | Sci Rep.) Bacteria killing increased with bigmouth buffalo age. The relationship between age and bacterial killing capacity in bigmouth buffalo from Lake Minnetaga (filled circles, solid line) and Artichoke Lake, Ottertail River, and Pelican Lakes (open circles, dashed line) with regression lines from the post hoc model with an additive effect of site and age. Bacterial killing capacity significantly increased with age.

Not only did the researchers observe evidence of lower chronic stress and more efficient immune function, but they also found no evidence that telomere length declines with age in this species. Telomere length shortens with age in humans and many other mammals and birds, and critically short telomeres are thought to lead to increased organismal aging and eventual death (mortality). Although telomere length was not correlated with age, bigmouth buffalo that had higher NLRs and had likely experienced more stress exposure or were more sensitive to it had shorter telomeres.

(Sauer et al., 2021 | Sci Rep.) Telomeres do not get shorter with the increasing bigmouth buffalo age. The relationship between age and relative telomere length measured from red blood cells of bigmouth buffalo. There was no significant relationship between age and telomere length.

What can this teach us about human aging?

Altogether, Sauer and colleagues found that older bigmouth buffalo have lower neutrophil to lymphocyte ratios, better immune function, and do not show any evidence of telomere shortening. These results match the idea that several physiological measures improve, rather than decline with age in this extremely long-lived fish.

“Our data are consistent with these criteria for negligible senescence as we observed many old, reproductive individuals with long telomeres, high condition values, and relatively efficient functioning stress responses and immune systems,” concluded Sauer and colleagues.

These results contradict many of the age-related patterns of senescence that have been observed in other vertebrates and may suggest a negligible rate of senescence in bigmouth buffalo. More research is needed to better understand how variation in life-history strategies influences age-related patterns in the immune systems of long-lived vertebrates.