Death is inevitable. But is it predictable? Some scientists think so. They say that experiments with fruit flies - fruit flies - have revealed a new distinct phase of life that heralds the approach of death. They call this stage of life the spiral of death and think that people can also experience it. Until 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 likelihood of death remains extremely low.
Along with the age of majority, or rather, with the achievement of puberty, adulthood begins. The likelihood of dying remains low when we begin our adult life - during this time we are in our prime and more likely to have children. But as time goes on, our bodies begin to age and degrade. With each city, the likelihood 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 identified the third phase of life through which the oldest members of our society go: late life.
Late life differs from the rest of adulthood by a unique mortality pattern. The annual rise in mortality rates that is characteristic of adulthood does not apply to later life. While a 60-year-old has a significantly higher chance of dying 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 are seeing these plateaus,” says Lawrence Mueller of the University of California at Irvine.
It is these mortality plateaus that are discussed to this day - they still have no single explanation. To shed light on this problem, Mueller and his colleague Michael Rose began looking for signs that other biological traits, apart from death rates, were leveling out towards the end of life. “We thought it 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.
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“We took 2,828 females and put each one individually in a vial with two males,” says Mueller. “Every day we moved each female to a new bottle and counted how many eggs they left behind. And they continued to do this until they all died."
These flies usually live for several weeks. “It was a massive experiment,” says Mueller. He admits that the experiment was also painstaking: moving so many flies day after day and counting their tiny eggs quickly gets tired. These were attended 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 off in an obvious way when the flies entered the "late life" phase.
When the scientists took a closer look at the data, they noticed something.
“I noticed that if I picked out females that were close to death and compared them with other females of the same age and, according to the database, who had several weeks more to live, there was a difference in fertility,” says Mueller.
Simply put, the fertility rate of flies - the number of eggs laid per day - plummeted two weeks before they died.
Even more surprising, this decline in fertility had nothing to do with the fly's age at death. If an elderly 60-day-old fly approached 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 years that followed, scientists looked for more evidence of this death spiral. In 2012, they found that male fruit flies experienced a similar decline in fertility a few days before death. This time, the repetitive data collection was done by PhD student Parvin Shahrestani.
“As the male gets older, his ability to fertilize females gets worse and worse,” says Müller. "But when males are about to die - at any age - their reproductive capacity was much lower than that of males of the same age who lived a few weeks longer."
Most recently, in 2016, Mueller and Rose drew 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 dataset showed a death spiral.
The two scientists and their colleagues even found that it was possible to predict to some extent when a fly would die by simply looking at its fertility in the previous three days and ignoring other data, including the fly's age. “We accurately predicted about 80% of deaths,” says Mueller.
Rose and Müller are not alone in developing this connection between fertility and death. James Curtsinger of the University of Minnesota conducted his own experiments on aging and death on fruit flies and found a decrease in fertility on the eve of death, which generally correlates with the findings of Mueller and Rose.
Curtsinger also found that this decline in fertility due to imminent death was independent of age: relatively young and old flies followed the same scenario.
However, Kertsinger's work differs from that of Mueller and Rose in several important ways. 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 distinct from fruit flies will experience such a decline in fertility. He also believes that the term "death spiral" is vague and ambiguous. Therefore, he developed his own terminology, which may be more to the liking of 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 am 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 the adult female can no longer lay a single egg. To understand the importance of this "egg zero day", one must 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. “The female lays about 1200 eggs in her life - that's half a meter of eggs if laid out in a line.”
In other words, the female fruit fly is an egg-laying machine. This is 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 - this indicates that something went wrong.
Kertsinger compares it to a car that runs out of fuel. He can drive a few more kilometers, but the first failures indicate a dangerous situation to the driver.
Kertsinger's work also revealed something else that Mueller and Rose's analyzes did not.
At the very end of the retirement phase, when fertility is low and death is inevitable, it becomes clear that flies reach a death plateau just like those associated with the end of life stage. “This is a completely new observation,” he says. "A 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 associated with age - but Kertsinger believes his new work shows that they - like death itself - may be more associated with fertility. This observation may require biologists to rethink their theories of aging.
Something, however, puzzles Kertsinger. Why is there this strong connection between fertility and death at all? Biologists have no explanation.
However, James Carey of the University of California at Davis thinks this simply reflects a well-studied idea: reproduction comes 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 reproductive systems of mice also changes their lifespan. They put old mice on an operating table and replaced their spent ovaries with equivalent organs for younger females - and the older mice lived longer than expected after surgery.
“There were indications that mice that received new ovaries had fewer heart problems than mice that received no new ovaries,” he says.
Curtsinger disagrees that people go through a "retirement" stage before dying, but Müller believes there is evidence that people doomed to die from natural causes experience a death spiral. In support of this, Müller cites another study conducted in Denmark in a nursing home.
The researchers took a group of ninety-year-old volunteers through a battery of tests to assess their strength, coordination, and intelligence. A few years later, they returned to the nursing home to find out who died and who is still living. For the most part, people who died did poorly on tests, Mueller said. On the eve of death, a decrease in physiological capabilities was observed.
What interests the scientist more is that working with fruit flies can identify strategies to prevent this cycle of death, so that it starts in a few days, not weeks.
It is hoped that such work may provide new hints on how to save people from the 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 while Mueller and Rose think they have found a fourth stage of life, in the long run they hope to rid people of it, or at least reduce it as much as possible.
ILYA KHEL