Dayton Kelly

Blowing away long held beliefs of how inheritance operates in humans, comes a new theory that suggests your everyday life may be modifying the set of genetic instructions you transmit to your offspring. That is, physical exercise and a healthy diet prior to impregnation or fertilization (in the case of males) could have lasting effects on the health of offspring (Gapp & Bohacek, 2017). Further, it could improve health in your offspring’s offspring and the generations following. This is the theory of transgenerational epigenetic inheritance. It describes the inheritance of characteristics through multiple generations by factors other than DNA (Holliday, 2006; Gapp & Bohacek, 2017).

A Primer on DNA

For those unfamiliar with genetics, DNA is the medium through which parents pass their genetic information to their children (Holliday, 2006). It is a long molecule that stores information using a four-letter sequence much like a computer stores information in a binary code of ones and zeros. To allow this template that builds a human to pass faithfully through thousands of generations, DNA is a relatively static material. We know this static nature is important because errors in this sequence can produce disease in humans (Riordan, et al., 1989; Holliday, 2006). Thus, it is sensical, from an evolutionary standpoint, that this sequence in our sperm and eggs remains protected and unchanged by our daily lives.

This theory of DNA, as a medium of passing information to our offspring, complements quite well the traditional views of inheritance we have held dear. Namely, that children are the product of the instructions that built their two parents. However, it is quickly becoming clear that this does not explain the entire picture of how inheritance works.

DNA Sequencing

After the sequence of DNA held in human cells was decoded in 2003, we quickly realized that the basic sequence of DNA was insufficient to explain the complexity of humans (Holliday, 2006). Instead, it seemed that the sequence needed to be controlled and regulated in how it was read by cellular machinery (Holliday, 2006). Further, this control, which we now call epigenetics, needed to be dynamic to a number of factors including the environment and conditions with the body. What is particularly interesting is that this control has been shown to be flux with elements of daily living in humans. And, now, with transgenerational epigenetic inheritance, possibly capable of being passed through generations (Gapp & Bohacek, 2017).

The passage of control through generations had been, for many years, considered to be limited in humans (genomic imprinting was accepted but little else; Holliday, 2006; Gapp & Bohacek, 2017). It is only recently, with the discovery of a new mechanism (noncoding RNA) through which this inheritance may operate that such a manner of inheritance has become plausible in our species (Gapp & Bohacek, 2017). Demonstrations show this mechanism as a causal in other mammals. But, to date, research is only heavily suggestive in humans largely due to ethical restraints (Gapp, et al., 2014; Gapp & Bohacek, 2017).

Epigenetic Inheritance

The Epigenetic Inheritance Study

In an experiment where mice were fed a high fat diet for four weeks and their sperm harvested to impregnate healthy female egg cells, high fat diet progeny were shown to display greater rates of diabetic symptoms than progeny spawned from control mice (Chen, et al., 2016). In a similar experiment, mice administered a stress hormone over 6 weeks produced progeny that displayed anxiety and depressive-like symptoms relative to control progeny (Short, et al., 2016). After analysis of the sperm and egg, both studies were able to convincingly argue that noncoding RNA was the responsible molecule inducing these effects (Chen, et al., 2016; Short, et al., 2016).

Takeaways

So how does this affect you? Both diet and exercise have been shown to exert epigenetic effects not only in mice, but also in humans (Barrès & Zierath, 2016). If these epigenetic effects are inherited, as research is now suggesting, this could be significant. Your diet and exercise in the years before you have children could improve their health. While many elements of this theory remain to be elucidated, it provides one more excuse to exercise and live healthy. Perhaps one day your children will be thanking you for all of those HIIT workouts you are putting in and years of living healthy!

References

Barrès, R., & Zierath, J. R. (2016). The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nature Reviews Endocrinology, 12(8), 441. Retrieved from https://www.nature.com/articles/nrendo.2016.87.

Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., . . . Qian, J. (2016). Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science, 351(6271), 397-400. doi: 10.1126/science.aad7977.

Gapp, K., & Bohacek, J. (2017). Epigenetic germline inheritance in mammals: looking to the past to understand the future. Genes, Brain and Behavior, doi: 10.1111/gbb.12407.

Gapp, K., Jawaid, A., Sarkies, P., Bohacek, J., Pelczar, P., Prados, J., . . . Mansuy, I. M. (2014). Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature neuroscience, 17(5), 667. doi: 10.1038/nn.3695.

Holliday, R. (2006). Epigenetics: A historical overview. Epigenetics, 1(2), 76-80. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17998809.

Riordan, J. R., Rommens, J. M., Kerem, B. S., Alon, N., Rozmahel, R., Grzelczak, Z., . . . Chou, J. L. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science, 245(4922), 1066-1073. Retrieved from http://cbm.msoe.edu/markMyweb/ggpmResources/documents/cftr_gene.pdf.

Short, A. K., Fennell, K. A., Perreau, V. M., Fox, A., O’Bryan, M. K., Kim, J. H., . . . Hannan, A. J. (2016). Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Translational psychiatry, doi: 10.1038/tp.2016.109.




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