Maternal Age Effects: A Reversible Biological Imprint

A groundbreaking discovery has revealed that a mother’s age can leave a reversible biological imprint on her offspring, which may echo across multiple generations. This phenomenon, known as maternal age effects, is a widespread phenomenon observed in humans and many other animal species.

According to Kristin Gribble, an associate scientist at the Bay Paul Center at the Marine Biological Laboratory, maternal age effects are incredibly common, from invertebrates to 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.

To investigate how information about maternal age is passed to offspring, Gribble’s laboratory studies rotifers, tiny aquatic animals that reproduce rapidly and are well-suited for laboratory experiments. Understanding the mechanism in these simple invertebrates can help us understand how maternal age effects occur in people as well.

Research on rotifers has led the team to an unexpected possibility: maternal age effects may be controlled by epigenetic processes that change how genes are used rather than by mutations that alter the underlying DNA sequence. Postdoctoral scientist Alyssa Liguori’s work examined two different genotypes from the same rotifer species and found that the effects associated with maternal age did not become progressively stronger with each generation. Instead, those effects could be reversed within a single generation.

This rapid reversal argues against the idea that maternal age effects are primarily caused by the gradual buildup of cellular damage or DNA mutations associated with aging, as many researchers had previously suspected. The findings instead point toward an epigenetic process involving histone modifications. These modifications can influence whether genes are switched on or off.

Gribble’s team is now testing whether histone modifications are responsible for the maternal age effects observed in the rotifers. She is also considering whether mitochondrial DNA, which is generally inherited from the mother, could play a role in transmitting information about maternal age from moms to offspring.

Genetic differences may also determine how strongly offspring are affected by an older mother. Gribble suggests that there may be gene variants that are protective of negative effects of advanced maternal age. In one of their strains, they saw that offspring from older mothers had a longer lifespan, implying a genetic mechanism may be involved in that beneficial effect.

The research highlights an important complication: although advanced maternal age is often associated with harmful outcomes, genetic variation may sometimes reduce those effects or even produce benefits. This finding has significant implications for our understanding of maternal age effects and their role in shaping the biology of offspring.

A major evolutionary puzzle is why maternal age effects remain so widespread. Offspring born to older mothers often live shorter lives, reproduce less, and have lower evolutionary fitness. In theory, natural selection might be expected to gradually remove traits that produce such disadvantages. Yet maternal age effects continue to appear across an extraordinary range of species.

Gribble thinks part of the explanation may be that natural selection becomes weaker later in an organism’s life. Selective pressure is much lower at advanced ages, particularly in rotifers, which are geared to do most of their living and reproducing very young. By the time female rotifers reach advanced ages, they have already produced most of their offspring, resulting in less evolutionary pressure favoring traits that help older females produce especially fit offspring.

The research suggests that an individual’s biology may reflect more than the DNA inherited at conception. Conditions experienced by previous generations could also matter. This has significant implications for our understanding of human health and may contribute to future approaches in precision medicine.

Gribble’s team is now working to understand how biological information can travel beyond a single generation. She wants 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.