Exercise Creates Tiny Genetic Changes in the Brain That Are Passed From Father to Son

A positive perception of regular exercise may be one of the more lasting gifts a parent can give their children. But there’s good news for those of us who don’t embrace the idea of working out, too. A study released Monday shows that if a parent spends their life regularly exercising, those genes are passed onto their children.

José Luis Trejo, Ph.D., a cell biologist at the Cajal Institute in Madrid, explains in his study that a new wave of research is investigating how lifestyle choices — both good and bad — can cause tiny genetic changes that end up getting passed on through generations.

The study, published in in the Proceedings of the National Academy of Sciences, was performed on mice and focuses on exercise as its “lifestyle choice.”

Trejo’s research shows that fathers who worked out tended to pass on exercise-related benefits, like certain patterns of gene expression in the brain, on to their offspring. Those patterns, Trejo tells Inverse, led to improved performance on learning and memory tasks in mouse offspring who had athletic fathers.

“It is known that the negative effects are inherited from parents to the progeny, for example, because of stress,” Trejo tells Inverse. “Only a few cues existed that the positive effects might be the same, in this case because of moderate exercise.”

Benefits Passed Down From Father to Child 🐁

To test if positive effects might be passed down to the next generation, Trejo had a group of mice undertake an object recognition test intended to test short- and long-term memory. He then bred a generation of offspring. Some of those mouse fathers performed a six-week exercise regimen, spawned a new round of offspring, and then took another, similar memory test. While tests of memory or intelligence in mice are a far cry from humans, Trejo did find some intriguing patterns.

After the paternal workout plan ended, these newly athletic mouse dads improved their performance memory exams compared to their earlier scores. Exercise has also been shown to increase memory in humans, too. Crucially, the mouse brains also showed small molecular markers of change that may underlie the change in memory test performance.

Specifically, the newly athletic mouse dads were expressing different genes in the hippocampus (an area of the brain involved in learning), and showed more activity in the mitochondria of certain cells within the hippocampus.

Trejo also saw increases in a small population of certain cells in that brain region as well, which means that the mice seemed to be producing new brain cells. That’s actually a controversial idea — only recently have we begun to embrace the idea that the adult brain can grow new cells.

Mice Born of Athletic Dads Did Significantly Better on Memory Tests🐁

Trejo’s paper shows that many of these brain-related changes were actually carried over into their children, too. Mouse litters born from athletic dads performed significantly better on memory tests than their siblings born before their dads underwent the workout regimen.

The mice born from newly athletic fathers showed small increases in certain cell populations in the brain and showed different patterns of gene expression in the brain compared to their siblings. 

“We have demonstrated that the characters acquired by the runner parents: increased neurogenesis, increased activity of mitochondria, change in the gene expression pattern, are inherited by the progeny although they are sedentary,” Trejo says. “All this has led to the litters to have inherited the greater capacity of learning and memory of the running parents.”

How Are These Changes Passed Down? MicroRNAs🐁

In the paper, Trejo presents an idea that these small, exercise-induced changes in the brain are passed from father to child through microRNAs. MicroRNAs, are coding pieces of genetic material that help regulate gene expression and are also carried as payloads in sperm.

“The paternal sperm microRNAs of exercised fathers could well be originating the changes we observed here in mitochondria, neurogenesis, and behavior,” they write. In other words, those microRNAs, modified by dad’s exercise regime, end up regulating certain populations of genes in the brains of their sedentary children.

"All this has led to the litters to have inherited the greater capacity of learning and memory of the running parents.”

Trejo isn’t the first to suggest that dad’s lifestyle choices may be passed on to future generations because of slight changes in microRNA. A 2016 study also done in mice found that obese mice tended to have different compositions of microRNA in their sperm, which “reprogrammed embryonic development” and hampered the metabolic health of their offspring.

Another mouse study published in 2016 in Scientific Reports also shows that diet-induced obesity changed the microRNA content of sperm, which was linked to the development of cancer in progeny. Those authors explained that obesity during the time of conception can “epigenetically reprogram father’s germline” — which means that it can cause changes in genetic material than can be passed on.

That body of literature paints a bleak picture about the effects of lifestyle choices on microRNA. Trejo’s paper brightens the outlook considerably. He presents evidence that positive lifestyle choices may also “reprogram that father’s germline” — and in this case, cause ripple effects on the brain that pass from father to child.

Abstract: Physical exercise has positive effects on cognition, but very little is known about the inheritance of these effects to sedentary offspring and the mechanisms involved. Here, we use a patrilineal design in mice to test the transmission of effects from the same father (before or after training) and from different fathers to compare sedentary- and runner-father progenies. Behavioral, stereological, and whole-genome sequence analyses reveal that paternal cognition improvement is inherited by the offspring, along with increased adult neurogenesis, greater mitochondrial citrate synthase activity, and modulation of the adult hippocampal gene expression profile. These results demonstrate the inheritance of exercise-induced cognition enhancement through the germline, pointing to paternal physical activity as a direct factor driving offspring’s brain physiology and cognitive behavior.