Shorten the death spiral

Can we predict when we will die?

Colin Barras, BBC: Can we predict when we will die? Translation: Ilya Khel, Hi-News  

Death is inevitable. But is it predictable? Some scientists think so. They say that experiments with fruit flies have revealed a new separate phase of life that heralds the approach of death. They call this stage of life the death spiral and think that people can also experience it. Even 25 years ago, biologists assumed that life has two main phases: childhood and adulthood. We can all recognize this division. Childhood is characterized by rapid growth and development and ends with puberty. During this phase, the probability of death remains extremely low.

Together with adulthood, or rather with the achievement of puberty, adulthood begins. The probability of death remains low when we begin our adult life – at this time we are in the prime of life and are more likely to have children. But as time goes on, our bodies begin to age and degrade. Every year the probability of death increases – slowly at first, and then faster and faster as we get older and older.

In the early 90s, scientists realized that life has another part. They have identified the third phase of life that the oldest members of our society go through: later life.

Later life is distinguished from the rest of adult life by a unique mortality structure. The annual increase in mortality rates, which is a characteristic feature of adulthood, does not apply to later life. If a 60-year-old has a significantly higher chance of imminent death than a 50-year-old, a 90-year-old has about the same chance of dying as a 100-year-old.

"The death rate is leveling off, and you see these plateaus," says Lawrence Mueller of the University of California at Irvine.

It is these plateaus of mortality that are being discussed to this day – there is still no single explanation for them. To shed light on this problem, Mueller and his colleague Michael Rose began to look for signs that other biological features, not counting mortality rates, are leveled by the end of life. "We thought that there might be the same pattern as reproduction or female fertility (fertility)," he says.

They began to study this problem using the example of a favorite set of laboratory animals – fruit flies drosophila.

"We took 2,828 females and placed each of them individually in a bottle with two males," says Muller. "Every day we moved each female to a new bottle and counted how many eggs they left. And they kept doing it until they all died."

Usually these flies live for several weeks. "It was a massive experiment," says Mueller. He admits that the experiment was also painstaking: moving so many flies from day to day and counting their tiny eggs – you get tired of it quickly. These were handled by Rose's graduate student, Cassanda Rauser, and dozens of students.

And after all these efforts, the results initially seemed disappointing. The birth rate did not level out in an obvious way when the flies entered the "late life" phase.

When scientists took a closer look at the data, they noticed something.

"I noticed that if I isolated females who were close to death and compared them with other females of the same age and, as it followed from the database, who had a few weeks more to live, there was a difference in fertility," says Muller.

Simply put, the birth rate of flies –the number of eggs laid per day–plummeted two weeks before their death.

Even more surprisingly, this decrease in the birth rate had nothing to do with what the age of the fly was at death. If an elderly 60-day–old fly was approaching death, its fertility rate dropped sharply - just like the fertility rate of 15-day-old flies, which, as it turned out, were on the verge of premature death.

It was a universal feature of life, a new fourth phase that was different from childhood, adulthood or later life. Mueller and Rose called it the "death spiral." It was 2007; in the following years, scientists were looking for more evidence of this death spiral. In 2012, they found that male fruit flies experience a similar decline in fertility a few days before death. This time, graduate student Parvin Shahrestani was engaged in repeated data collection.

"As the male gets older, his ability to fertilize females gets worse and worse," says Muller. "But when males are about to die–at any age–their reproductive ability was much lower than that of males of the same age who lived a few weeks longer."

More recently, in 2016, Muller and Rose extracted data from a series of experiments investigating the longevity and fertility of fruit flies, which scientists worked on in four independent laboratories. Again, the combined data set showed the presence of a death spiral.

Two scientists and their colleagues even found that to a certain extent it is possible to predict when a fly will die by simply looking at its fertility in the previous three days and ignoring other data, including the age of the fly. "We accurately predicted about 80% of deaths," says Mueller.

Rose and Mueller are not alone in developing this link between fertility and death. James Kertsinger from the University of Minnesota conducted his own experiments in the field of aging and death on fruit flies and revealed a decrease in fertility in the run-up to death, which generally correlates with the conclusions of Muller and Rose.

Kertsinger also found that this decline in fertility due to imminent death does not depend on age: relatively young and old flies followed the same scenario.

However, the work of Kertsinger differs from the work of Mueller and Rose in several important points. For example, he does not believe that his observations indicate a separate and universal fourth phase of life – he does not believe that humans or other species that are biologically different from fruit flies will experience a similar decrease in fertility. He also believes that the term "death spiral" is vague and ambiguous. Therefore, he has developed his own terminology, which may appeal more to biologists.

"When I was 20, I researched the sex ratio; when I was 40, I started working on aging – now I'm 65 and I'm working on a new biological concept that I call retirement," he says.

This "retirement" is easy to see in fruit flies. It begins on the day when an adult female can no longer lay a single egg. To understand the importance of this "zero egg day", you need to remember the fertility of the female fruit fly. "The fly is 2.5 mm long, and the fruit fly egg is 0.5 mm long," says Kertsinger. "A female lays about 1,200 eggs in her lifetime–that's half a meter of eggs if you put them in a line."

In other words, the female fruit fly is an egg–laying machine. It's the only thing on her mind. If a fly doesn't lay a single egg on a particular day – even if it starts laying eggs again the next day – it indicates that something went wrong.

Kertsinger makes a comparison with a car that runs out of fuel. He can drive a few more kilometers, but the first failures indicate to the driver a dangerous situation.

Kertsinger's work also revealed something else that Mueller and Rose's analyses did not.

At the very end of the retirement phase, when the level of fertility is low and death is inevitable, it becomes clear that the flies reach the plateau of mortality exactly the same as those associated with the "end of life" stage. "This is a completely new observation," he says. "The mortality plateau is not a feature of old age, it can appear in middle age or at a young age."

The general consensus now is that mortality plateaus are age–related–but Kertsinger believes his new work shows that they–like death itself- may be more related to fertility. This observation may require biologists to revise their theories of aging.

Something, however, puzzles Kertsinger. Why is there such a strong connection between fertility and death at all? Biologists have no explanation.

Nevertheless, James Carey from the University of California at Davis believes that all this simply reflects a well-studied idea: reproduction takes place at the cost of the health of parents, especially mothers. Women face dental problems, for example, as a consequence of having many children.

More than a decade ago, Carey and his colleagues showed that modifying the reproduction systems of mice also changes their lifespans. They put old mice on the operating table and replaced their spent ovaries with equivalent organs of younger females – and the old mice lived longer than expected after surgery.

"There were signs that mice who received new ovaries had fewer heart problems than mice who did not receive new ovaries," he says.

Kertsinger does not agree that people go through the "retirement" stage before death, but Muller believes that there is evidence that people doomed to death by natural causes experience a death spiral. In confirmation of this, Muller cites another study conducted in Denmark in a nursing home.

The researchers put a group of ninety-year-old volunteers through a battery of tests to assess their strength, coordination and mental abilities. A few years later, they returned to the nursing home to find out who had died and who was still living. The people who died, for the most part, did not pass the tests well, says Mueller. In the run-up to death, there was a decrease in physiological capabilities.

What interests the scientist more is that working with fruit flies can reveal strategies to prevent this cycle of death, so that it begins in a few days, not weeks.

It is hoped that such work may give new hints on how to save people from a long and slow decay before death. It would be interesting to shorten the death spiral so that you stay as healthy as others until you die.

So although Muller and Rose think they have found the fourth stage of life, in the long run they hope to rid people of it or at least reduce it as much as possible.

Portal "Eternal youth" http://vechnayamolodost.ru  28.06.2016