Understanding how maternal age impacts offspring health across different species

In humans and many other animals, a mother's age can affect the physical and behavioral characteristics of the next generation. Scientists call these changes maternal age effects, and while they are widespread across the animal kingdom, researchers still don't fully understand how or why they occur.

Maternal age effects are incredibly common, from invertebrates up through humans, elephants, other primates and other mammals. Nearly all forms of life show some level of maternal age effect, and most are negative effects caused by advanced maternal age."

Kristin Gribble, associate scientist, Bay Paul Center, Marine Biological Laboratory

Gribble's lab is using rotifers-tiny aquatic animals that reproduce quickly and are easy to study-to uncover the biological mechanism that transmits information about a mother's age to her offspring. "Understanding the mechanism in these simple invertebrates can help us understand how maternal age effects occur in people as well," she said. By studying rotifers, her lab has made a surprising discovery, that maternal age effects are likely driven by an epigenetic mechanism-a change in how a gene is expressed, rather than a mutation in the DNA sequence itself.

Research done in Gribble's lab by postdoctoral scientist Alyssa Liguori, who is now an assistant professor at SUNY-New Paltz, showed that in two different genotypes of the same species of rotifer, maternal age effects didn't increase with every generation. Instead, they could be rapidly reversed in a single generation, implying that maternal age effects are not caused by the gradual accumulation of cellular damage or DNA mutations associated with advanced age, like many previously thought. Instead, the inherited effects may be the result of an epigenetic mechanism known as histone modifications, which can turn gene expression on or off.

Her lab is now investigating whether these histone modifications are responsible for the maternal age effects they have observed, and Gribble is also considering the potential role of mitochondrial DNA, which is typically passed from the mother, "in transmitting information about maternal age from moms to offspring."

Her lab is also interested in how the severity of maternal age effects in offspring may depend on genetic variation. "There are likely gene variants out there that are protective of negative effects of advanced maternal age," Gribble said. "In one of our strains, we saw that offspring from older mothers had a longer lifespan, implying a genetic mechanism may be involved in that beneficial effect."

One of the biggest unanswered questions is why maternal age effects persist at all. Because offspring of older mothers often have shorter lifespans, reproduce less and are less evolutionarily fit, scientists would expect natural selection to eliminate these effects over time. Instead, maternal age effects are found across a remarkable diversity of species.

Gribble suspects one reason maternal age effects persist is that natural selection weakens later in life. "Selective pressure is much lower at advanced ages, particularly in rotifers which are really geared to do most of their living and reproducing very young," she said. By the time females reach old age they have already produced most of their offspring, so there is less evolutionary pressure acting on them to produce fit offspring.

What excites Gribble most is uncovering how information is passed from one generation to the next. "I want to know how it happens that information about a grandmother or great grandmother's environment can affect the phenotype of her grandchild or great grandchild," she explains.

Understanding how maternal effects are transmitted across generations could also improve scientists' understanding of human health and inform future approaches to precision medicine. "It's not just about what's in your genome as an individual," Gribble said, because "your health potentially depends on the health and environment of your mom and grandmother and great grandmother."