Scientifically Speaking | Why do some animals live longer than others?

New research shows that animal lifespans are highly correlated to the number of somatic mutations in similar cells that each possesses. What does this mean?

A giraffe is 40,000 times the size of a mouse, and a human lives 30 times longer. Giraffes, cows, and horses weigh more than humans, but they all live shorter lives. These observations beg the question: Why do some animals live longer than others?

Earlier work had shown that somatic mutations in specific cells increase at a constant rate in humans until death. This conclusion has been extended to other animals in the recent study.(Shutterstock)

The naked mole-rat lives longer than one might expect based on its size. On a cellular level, it has developed mechanisms that make it cancer-resistant. It is around 23,000 times smaller than a giraffe, but both animals live to be about the same age (around 20-30 years). As such, it’s not the size of the animal alone that predicts the lifespan of members of a species.

New research published in Nature on April 13, 2022, by Alex Cagan and his colleagues at Wellcome Sanger Institute in the United Kingdom shows that animal lifespans are highly correlated to the number of somatic mutations in similar cells that each possesses.

Somatic mutations are changes to DNA that occur over time in cells of the body. Some of these mutations cause cancer, but the vast majority are harmless or have no known function.

Earlier work had shown that somatic mutations in specific cells increase at a constant rate in humans until death. This conclusion has been extended to other animals in the recent study.

There’s long been interest in determining the effect of mutations on ageing and lifespan. But there have been technical challenges to rapidly comparing mutation rates in cells across different animals. In recent years, DNA sequencing technologies have advanced to make these comparisons feasible.

In the present study, the authors decided to look at one kind of cells (called intestinal crypt cells) found in 16 different kinds of mammals of differing sizes and lifespans. They collected intestinal crypt cell samples from mice, lions, tigers, giraffes, and naked-mole rats, among other animals. They chose to look at the same kind of cells in different animals because even different cell types in one kind of an animal can have some differing mutation rates. Human cells, for example, can vary from 20 to 50 mutations per year on average depending on the cell type.

What the researchers found is that human intestinal crypt cells accumulate close to 50 mutations a year, while mice accumulate around 800. What is perhaps most astonishing is that despite vastly different sizes of animals and differing lifespans, the total number of mutations that can accrue in different animals falls in a narrow range.

Simply put, what this means is that as a general rule shorter-lived animals accrue mutations at a faster rate than longer-lived ones. This is an incredible correlation that immediately suggests that there’s a mutational clock ticking away at different speeds in different animals but getting to roughly the same “stroke of midnight” signalling end of life.

The new research shows that mutations accumulate like clockwork over time in different cells of different animals. In the case of the naked mole-rat and the giraffe, they both have similar lifespans and as predicted roughly the same rate of accumulating somatic mutations.

Lead author, Cagan summed up the future directions of the study. “To find a similar pattern of genetic changes in animals as different from one another as a mouse and a tiger was surprising. But the most exciting aspect of the study has to be finding that lifespan is inversely proportional to the somatic mutation rate. This suggests that somatic mutations may play a role in ageing, although alternative explanations may be possible. Over the next few years, it will be fascinating to extend these studies into even more diverse species, such as insects or plants.”

But though there’s strong evidence to suggest there’s a possible causal link between mutations and lifespans, there may be more yet to be discovered. The authors of the paper also note that it isn’t just the number of mutations in cells that lead to ageing, but very specific ones in places that are disadvantageous to the organism.

Then, other factors relate to the ageing of cells such as the ability to create new proteins and repair damaged ones. There’s also a great deal of interest in telomeres, which cap the ends of chromosomes; they’ve been compared to the protective ends of shoelaces. The shortening of telomeres is also linked to ageing.

I’m also curious if it might ever be possible to use somatic mutations to predict lifespan within a species. For example, could finding differences in mutations help to calculate a person’s life expectancy? And if so, will it ever be possible to slow down the rate of mutations to reduce cancer risk and increase lifespan?

Many factors influence ageing and lifespan, but if there is a biological limit to the number of mutations cells can accumulate before malfunctioning that is preserved across different animals, that would mean that humans are not exceptional animals. But it also opens up the intriguing possibility of lifespan extension by enhancing DNA repair mechanisms that fix mutations.

Anirban Mahapatra, a scientist by training, is the author of COVID-19: Separating Fact From Fiction

The views expressed are personal