DW
December 15, 2023
The genes that boost fertility mean you're more likely to die younger, according to a new study.
December 15, 2023
The genes that boost fertility mean you're more likely to die younger, according to a new study.
A new study suggests genetic variants involved in reproduction also contribute to premature aging in humans
Image: Fotolia/Prodakszyn
One of the puzzles of evolution is why we peter out into old age once we can no longer reproduce.
Now, scientists believe that aging may actually be a consequence of how we evolved to reproduce, and it's all a result of natural selection over millions of years.
A study analyzing the genes of 276,406 UK Biobank participants found that people carrying gene variances promoting reproduction are less likely to survive to old age.
"We confirm a hypothesis called the antagonistic pleiotropy hypothesis, which says that mutations promoting reproduction are more likely to reduce life span," said Jianzhi Zhang, of the University of Michigan in the US and senior author of the study in the journal Science.
According to the research, people carrying genetic variances promoting reproduction were more likely to die by the age of 76. The study also shows that genetic variances promoting reproduction increased over generations from 1940 to 1969, meaning humans are still evolving and strengthening the trait.
One of the puzzles of evolution is why we peter out into old age once we can no longer reproduce.
Now, scientists believe that aging may actually be a consequence of how we evolved to reproduce, and it's all a result of natural selection over millions of years.
A study analyzing the genes of 276,406 UK Biobank participants found that people carrying gene variances promoting reproduction are less likely to survive to old age.
"We confirm a hypothesis called the antagonistic pleiotropy hypothesis, which says that mutations promoting reproduction are more likely to reduce life span," said Jianzhi Zhang, of the University of Michigan in the US and senior author of the study in the journal Science.
According to the research, people carrying genetic variances promoting reproduction were more likely to die by the age of 76. The study also shows that genetic variances promoting reproduction increased over generations from 1940 to 1969, meaning humans are still evolving and strengthening the trait.
"This shows the evolutionary pattern of high reproduction and low survival [and vice versa] is still visible in modern humans. Our gene variants are the product of hundreds of thousands of years of evolution. What's surprising is that despite our far better health than ever before, this pattern is still visible," said Steven Austad, an expert in aging research at the University of Alabama at Birmingham, in the US, who wasn't involved in the study.
Why aren't humans more fertile in old age?
Scientists have been puzzling over the evolutionary origins of aging for some time. It's unclear why, from an evolutionary perspective, our reproductive performance declines with age. Surely being more fertile in old age would be evolutionary advantageous, giving us more time to pass on our genes?
Not so, according to the antagonistic pleiotropy hypothesis. The hypothesis states that the benefits of fertility in early life are responsible for the dreadful cost of aging. This new study now provides robust evidence from a huge sample of humans to back it up.
"This idea is that some traits [and genetic variants that cause them] are important when we are young, helping us grow strong and be fertile. But, when we get older, those same traits can start causing problems and make us fragile and unhealthy. It's like some mutations having two sides: a good side when we're young, and a not-so-good side when we're old," said Arcadi Navarro Cuartiellas, a geneticist at the Pompeu Fabra University in Barcelona, Spain who was not involved in the study.
One example is the effects of menopause and fertility loss in women. Eggs, sometimes called ova, deplete during a woman's lifetime. This makes a person more fertile in young adulthood, but results in loss of fertility later in life through menopause.
Genetic variants that increase the chances of having twins may also increase with aging
Pavlo Gonchar/ZUMAPRESS/picture alliance
Biologists think the benefits of regular cycles for reproduction may outweigh the cost of infertility in older age. The downside is that menopause speeds up aging.
"Another example is, say, a gene variant enhances fertility so that a woman is more likely to have twins. Evolutionarily that might be advantageous, because she will potentially leave more copies of that variant than women who have single babies. But having twins leads to more wear and tear on her body so she ages more quickly. That would be an antagonistically pleiotropic process," said Austad.
The converse is true as well. A gene variant that reduces fertility early in life will likely cause a person to have fewer or no children, so that the person ages more slowly, Austad added.
But how does the environment affect aging?
The antagonistic pleiotropy hypothesis does have its criticisms, however. For one, it doesn't account for the huge effects of the environment and socioeconomic changes on aging, and nor does this study.
After all, humans are living longer than ever before in history, and it's mostly due to better health care rather than genetic evolution.
"These trends of phenotypic changes are primarily driven by environmental shifts including changes of lifestyles and technologies," said Zhang. "This contrast indicates that, compared with environmental factors, genetic factors play a minor role in the human phenotypic changes studied here."
Austad said a surprising outcome of the study was that reproductive genes had such a strong and observable effect on aging.
"Environmental factors are so important that I'm really surprised patterns [observed in this study] were still visible despite their importance. I think that is the advantage of having hundreds of thousands of individuals in a study," he said.
Research could have implications for aging
The antagonistic pleiotropy hypothesis had "mountains of evidence before this paper but not for humans," according to Austad. But the research in humans, and with such a huge sample size, means the study could be important for understanding aging-related diseases.
"Ultimately, some of these variants could now be examined to see if they link to certain later life health problems, so that those problems can be monitored closely and possibly prevented," Austad told DW.
Scientists think the hypothesis could help explain why many serious genetic disorders are prevalent in our long evolutionary history.
Sickle cell anemia is a good example of antagonistic pleiotropy – whereby an inherited blood disorder which causes anemia actually evolved as a protective mechanism against malaria.
Biologists think the benefits of regular cycles for reproduction may outweigh the cost of infertility in older age. The downside is that menopause speeds up aging.
"Another example is, say, a gene variant enhances fertility so that a woman is more likely to have twins. Evolutionarily that might be advantageous, because she will potentially leave more copies of that variant than women who have single babies. But having twins leads to more wear and tear on her body so she ages more quickly. That would be an antagonistically pleiotropic process," said Austad.
The converse is true as well. A gene variant that reduces fertility early in life will likely cause a person to have fewer or no children, so that the person ages more slowly, Austad added.
But how does the environment affect aging?
The antagonistic pleiotropy hypothesis does have its criticisms, however. For one, it doesn't account for the huge effects of the environment and socioeconomic changes on aging, and nor does this study.
After all, humans are living longer than ever before in history, and it's mostly due to better health care rather than genetic evolution.
"These trends of phenotypic changes are primarily driven by environmental shifts including changes of lifestyles and technologies," said Zhang. "This contrast indicates that, compared with environmental factors, genetic factors play a minor role in the human phenotypic changes studied here."
Austad said a surprising outcome of the study was that reproductive genes had such a strong and observable effect on aging.
"Environmental factors are so important that I'm really surprised patterns [observed in this study] were still visible despite their importance. I think that is the advantage of having hundreds of thousands of individuals in a study," he said.
Research could have implications for aging
The antagonistic pleiotropy hypothesis had "mountains of evidence before this paper but not for humans," according to Austad. But the research in humans, and with such a huge sample size, means the study could be important for understanding aging-related diseases.
"Ultimately, some of these variants could now be examined to see if they link to certain later life health problems, so that those problems can be monitored closely and possibly prevented," Austad told DW.
Scientists think the hypothesis could help explain why many serious genetic disorders are prevalent in our long evolutionary history.
Sickle cell anemia is a good example of antagonistic pleiotropy – whereby an inherited blood disorder which causes anemia actually evolved as a protective mechanism against malaria.
Zhang told DW that antagonistic pleiotropy may also be at play in Huntington's disease.
"Mutations causing Huntington's disease, a neurodegenerative disorder, also increase fecundity [the possible number of offspring produced]," Zhang said.
Mutations in the gene which causes Huntington's disease have also been hypothesized to lower rates of cancer.
Zhang said the paper could also have implications for the rising science of anti-aging.
"In theory, one could tinker with those antagonistically pleiotropic mutations to prolong life, but the downside would be reducing or delaying reproduction," said Zhang.
Edited by: Martin Kuebler
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