Researchers validate theory on ageing

Breaking new ground 26. aug 2021 4 min Research Director and Research Professor Stig William Omholt, Professor Emeritus and Affiliate Professor of Biogerontology Tom Kirkwood Written by Kristian Sjøgren

A theory on ageing identifies evolution as the primary reason why life cannot last forever.

People have been interested in ageing for as long as they have roamed the Earth.

We are born, we grow older, we die. This seems to be universal for all animals, but how quickly we progress from the beginning of life to the end still differs greatly. Some flies live for only a few days, mice manage a year or two, cats live for about 20 years and people can hold on to life for about 80 years.

For example, people and mice differin biology, and this difference makes the mice age much more rapidly than we do. We can therefore ask why mice do not live for 80 years like we do. After all, nature has figured out how to make organisms live that long.

We can also ask why humans cannot live forever. Some animals actually can.

Thomas Kirkwood, Professor Emeritus, Institute of Ageing, Newcastle University, United Kingdom and Affiliate Professor of Biogerontology, University of Copenhagen suggests that understanding ageing and the mechanisms behind requires us to understand the evolution underpinning the variation in lifespans.

“Ageing is a field that is of great interest to the natural sciences but also has immense sociological significance. The world is experiencing a demographic trend in which populations get older and older. This is of great importance to society and we therefore need to understand why ageing takes place at all,” explains Thomas Kirkwood.

Theory explains why animals have different life expectancy

Thomas Kirkwood and Stig Omholt, Research Director and Research Professor, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, have advanced a new theory to explain ageing specifically from an evolutionary perspective. The research has been published in the Proceedings of the National Academy of Sciences of the United States of America.

Although some cells can potentially live forever in our bodies and in nature and we therefore can also live forever, there must be a reason why this does not occur.

Thomas Kirkwood explains that this must be related to the fact that animals in the wild very rarely die from old age. They die from all sorts of other external causes. For example, they can be eaten by predators; the seasons are against them; they accumulate injuries such as broken bones over time; or one of the thousands of other causes.

When the chances of living to a ripe old age are so small, nature and evolution do not need to invest in the cellular mechanisms that can maintain cell functions year after year after year.

“The theory is that making mice or people live forever is not a priority. Evolution has chosen to invest resources in other aspects of life because this makes more sense than investing resources in immortality, since it will not happen anyway. From an evolutionary perspective, maintaining a fully functioning organism only makes sense for as long as it can reasonably be assumed that the organism will live,” says Thomas Kirkwood.

Mice have a short life because investing in longevity has no benefits

To understand why a mouse has only a short lifespan, we need to examine the external factors that influence its risk of dying.

A long life is very utopian if you are a mouse on the forest floor in an average forest which is full of animals that want to eat you, and where there are all sorts of other dangers, such as the weather or the seasons.

Mice rarely live longer than 1 year in the wild. In a laboratory, they can live for about 3 years. From an evolutionary viewpoint, it thus makes no sense for the mouse to expend precious resources in its 1-year life on maintaining its cells so that they do not grow old. These include repairing DNA or eliminating dangerous damage. Instead, allocating resources to functions in the body that make surviving until tomorrow or having more pups more likely is a much better investment.

“Allocating extra resources to reproduction is a good idea, but there is also a fundamental reason for reducing maintenance costs. Repairing consumes energy. Obtaining the necessary energy requires that the animal expose itself to dangerous environments. Using less energy reduces its risk of dying from environmental reasons. The core of this new study is to show how evolution favours cutting long-term maintenance to reduce the risk of death in the short term – even if this means ageing in the long term. Conserving energy reduces the risk of dying from external factors, which is the greatest threat to wildlife. Ageing is the price they have to pay,” explains Stig Omholt.

Evolution also explains why some animals live longer than others

According to the theory, the risk of dying from external factors should be associated with life expectancy, because investing in living longer is only worthwhile for animals if their risk of dying decreases.

One example that springs to mind is a mouse that evolves wings and thus becomes a bat. Escaping from the forest floor significantly reduces the risk of being eaten by predators.

Does this also mean that a bat can invest more resources in cellular maintenance and thus live longer?

Actually, it does. Bats can live for up to 20 years or longer, despite being no larger than mice. Investing in longevity is worthwhile because if they do not, they risk dying from old age before a predator bites them.

“Ageing is a trade-off to the risk of dying. Cell studies therefore show that cells from cows are better at taking care of themselves using various cellular maintenance mechanisms than cells from mice are. Human cells are even better at this than cows. Cells from animals with long lifespans are generally better at repairing themselves and their genetic material,” explains Thomas Kirkwood.

The theory answers several questions simultaneously

Thomas Kirkwood explains that this theory dispels the idea that we should focus on the concept of cellular mechanisms that are actually programmed on purpose to make cells function worse over time and lead to cell death or the death of the organism. Instead, we need to focus on the mechanisms that keep cells alive. Ageing is the result of an accumulation of somatic damage (damage to the cells).

Alzheimer’s is a typical age-related disease that occurs when enough damage has been done to brain cells. The same applies to cardiovascular disease.

Differences in the investment in reducing somatic damage are what separates human life expectancy from that of mice.

As Stig Omholt puts it, “The power of this theory is that it unifies two major questions in ageing research: why biology works the way it does and how it works. Ageing is a challenging feature in our present-day secure society, but it evolved for a positive reason.”

Thomas Kirkwood echoes this conclusion, “Once we know why ageing occurs, we will be better empowered to understand how it causes age-related frailty and diseases and what interventions might be possible. This is now an area of huge biomedical importance.”

Aging as a consequence of selection to reduce the environmental risk of dying” has been published in the Proceedings of the National Academy of Sciences of the United States of America. In 2018, the Novo Nordisk Foundation awarded a Challenge Programme grant for the project Harnessing the Power of Big Data to Address the Societal Challenge of Ageing, in which Thomas Kirkwood participated.

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