Every parent wants to provide whatever they can to help their child grow up happy and healthy. Most people will immediately think of things like a safe place to live, healthy food to eat, a good education, and so on. However, the very first thing that a parent provides is something much more fundamental: the genes that determine the biological makeup of their child. As I have written about before in this blog post, our gene DNA sequences determine the functions of the proteins, cells, tissues and organs that biologically define us. But we can’t change our DNA sequences (at least not yet, though maybe one day it will be possible through genome editing technology such as CRISPR/Cas9), so is there any way of controlling the genetic information we pass on to our children?
It has emerged over the past decade or more that children inherit far more than a combination of the genetic sequences of their parents. Genes can be switched on and off by a variety of mechanisms; some of these are behaviourally and environmentally modifiable, and can also be passed down through generations. The DNA that makes up genes and the structures that DNA binds to can be chemically tagged, or non-coding RNA molecules such as miRNA can alter and interfere with many stages of gene transcription and translation. The study of heritable changes in genes that do not involve alterations of DNA sequence is known as epigenetics.
It has long been known that maternal health is an important influence on an offspring’s lifelong health. This is intuitive, as maternal health is inextricably linked to the gestational environment in which a fetus develops. Prime examples of this are maternal obesity being a risk factor for obesity in the child, independent of genetics, and gestational diabetes, which epigenetically predisposes the child to obesity, diabetes, and cardiovascular disease later in life.
It has also emerged that paternal health at the time of conception is also critical to the lifelong health of offspring. For example, obese male mice (due to being fed a high fat diet) mated to normal weight female mice produce obese and insulin resistant male and female offspring. Even if those second generation mice were fed a normal diet, the obese phenotype could still be seen in females of the third generation – an epigenetic legacy of the diet of their “grandfathers”. Interestingly, short-term exercise programmes for obese male mice before mating reduced these intergenerational effects. Whether these sorts of effects can be reproduced in humans remains to be seen.
The target of most cardiovascular and metabolic disease treatments are those who already have or are at high risk of developing these conditions. However, the origins of these diseases may exist before the patient is even born, making prospective parents a potential target for preventative health measures such as exercise programmes.
Nathan Scrimgeour, Engineer at CERG