The concept of “transgenerational” genetic effects: Our decisions and actions taken today could affect our children and grandchildren as well as possible future generations.
Background:
This article addresses the fascinating connections observed between experienced environmental factors and changes in gene expression, observed in a current Swedish study as well as other interesting studies related to transgenerational genetic effects.
Questions:
1) Will actions that we take today, as individuals or as a society, affect how genes are expressed in our cells? Can an altered expression of genes be passed down to future generations? If so, how long does that impact last? How many generations might be impacted?
2) Do lifestyle, dietary choices, and life experiences make us and our descendants (first- and second-generation offspring) more or less vulnerable to certain diseases/conditions?
3) Can trauma in an individual’s lifetime cause genetic changes that can be passed down to future generations?
Analysis:
We cite an interesting and recent study by researchers at Stockholm University in Sweden (1). The goal was to investigate how hunger and malnutrition affected the subsequent three generations in the same community. The results are surprising: when a paternal grandfather had abundant food intake in his pre-pubertal years, his grandson’s lifespan was shortened by an average of 6 years. Further, this phenomenon was observed in male grandchildren, but not in female grandchildren. We found this to be fascinating!
The sample size of this study, encompassing 9,000 grandfathers and 11,000 grandchildren, provides a sample size (power) that is statistically significant; additionally, the study was controlled for confounding factors such as smoking and pesticide use. Of note, the shortened lifespan of grandsons was found to be primarily due to cancer.
Precisely why the abundance of food in the years immediately before puberty shortens the lifespan of grandsons requires further investigation. However, this study strongly suggests that transgenerational effects exist among us and our descendants.
It is easier to understand accepted Mendalian transmission of genetic material (2) since our children and grandchildren share a certain percentage of our DNA. However, the fact that our actions might affect our grandchildren is worth studying further as these factors may lie within our control. Of course this should not be confused with the discredited inheritable views of Lamarck (3, 4). Determining which factors are actionable provides an exciting opportunity to modify risks based on our actions for the potential benefit of future generations.
In relation to these considerations, there have been extensive scientific studies conducted over the past two decades into the genetic impact of a field called “Epigenetics” (5, 6). In order to get a better idea of what this field has to offer, it should be noted that “Epi” in this case refers to “general control of or influence over” (6). In other words, studies on the cellular modifications applied to DNA and proteins involved in the control of genetic expressions (6). The primary modification utilized in the cell is the chemical application of methyl groups (CH3) which can alter the configuration of DNA or protein and change their function (6). In doing so, the activity of DNA expression can be modified and as a result cellular activity and function changed. Why should this be important and how did it come about? The answers to these questions are much too involved for the present discussion. However, there is considerable scientific evidence obtained to suggest an evolutionary struggle taking place between eukaryotic cells (of which all higher organisms are made) and invading viral elements over millions of years. Since the successful genetic sequencing of the human genome (and those of many other animal genomes), it has become evident that a large portion of the 3 billion basepairs making up our genetic package (40% to 45%) is actually viral in nature (7, 8, 9). In order for us to become human and not a virus, the activity of those viral genes much be subdued. It is now thought that epigenetic activity is the primary means developed and used by eukaryotic cells to inactivate these viral genes in our genome (10).
In another 2013 experiment (11) at the Emory University’s Yerks National Primate Research Center, it was discovered that animals can pass on very specific information about a traumatic experience to their 1st generation (F1) and 2nd generation (F2) offspring. The original generation of mice was exposed to an odor coupled with a mild electric shock on the soles of their feet, which startled them. Then the same researchers tested the 1st generation and 2nd generation of the startled mice, and they found that both generations of mice inherited the same sensitivity to the odor and also flinched at the odor, although they had never received nor observed shocks to their feet (11).
These findings, coupled with evidence in other research (12 – 15), have led scientists to believe that generalized effects of diet, hormone changes, and trauma can be transmitted epigenetically. At the current time, it is unclear if these effects are reversible.
Over the last decade, there is developing consensus among researchers that how we live, what we eat, and certain events in our lives can affect which genes are expressed, and become more active or less active in our cells. The DNA itself does not change, but some genes may be activated or inactivated by environmental factors. This is significant, in that certain gene expressions can potentially impact vulnerability to certain diseases; there is also evidence that these changes can be inherited over several generations (16, 17).
Answers to our questions:
1) Will actions that we take today, as individuals or as a society, affect how genes are expressed in our cells? Can an altered expression of genes be passed down to future generations? If so, how long does that impact last? How many generations might be impacted?
Answer: Yes, very likely. It is unknown at this time how long the impact may persist and how many generations might be impacted.
2) Do lifestyle, dietary choices, and life experiences make us and our descendants (first- and second-generation offspring) more or less vulnerable to certain diseases/conditions?
Answer: Yes, potentially.
3) Can trauma in an individual’s lifetime cause genetic changes that can be passed down to future generations?
Answer: Yes, potentially.
Conclusion:
There is nothing really we can do to alter our existing DNA after we are born. However, we can, to a certain extent, understand the potential effects that our actions have on our descendants. Factors including diet, lifestyle, and environmental exposures can impact gene expression in current as well as future generations. Knowing the significance of these factors in changing outcomes for descendants can help facilitate healthy decision-making for individuals now and in the future.
Every individual will encounter traumatic events or harmful environmental exposures at some point during their lifetimes. Suffering these insults may have transgenerational impact, but that is not completely deterministic; harm to future generations is not a foregone conclusion. However, the understanding that current actions and exposures have the potential to affect future generations will present opportunities for quantifying these impacts in order to modify risk for both present and future generations.
Disclaimer:
This article does not constitute medical advice. Please consult your doctor for your specific situation. Lifestyle choices are individuals’ choices.
It is written by Eggschain editors, a) scientifically reviewed by Dr. Kenneth Drury, PhD, HCLD, who holds a Post-Doc in Molecular Function of Maturation Promoting Factor from University of California Berkeley, is b) medically reviewed by Dr. Carolyn Thompson who is a board-certified OB/gyn, FACOG MD in Medicine, and c) is also medically reviewed Hugh Taylor, MD, the Anita O’Keeffe Young Professor and Chair, Department of Obstetrics Gynecology and Reproductive Sciences at Yale School of Medicine and Chief of Obstetrics and Gynecology at Yale-New Haven Hospital. He is also Professor of Molecular, Cellular and Developmental biology at Yale University.
References:
1. Grandsons’ health at risk if grandpa ate well in his youth.This odd connection may be due to our genes being affected by the world around us. https://www.sciencenordic.com/food-forskningno-genes/grandsons-health-at-risk-if-grandpa-ate-well-in-his-youth/1461661
2. Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders Citation: Chial, H. (2008) Mendelian genetics: Patterns of inheritance and single-gene disorders. Nature Education 1(1):63. https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
3. Jean Baptiste Lamarck: Early Concepts of Evolution https://www.pbs.org/wgbh/evolution/library/02/3/l_023_01.html#
4. The History of Evolutionary Thought, UC Berkeley, Early Concepts of Evolution: by Jean Baptiste Lamarck
5. What is Epigenetics? https://medlineplus.gov/genetics/understanding/howgeneswork/epigenome/
6. Epigenetics: The Science of Change. Bob Weinhold. Environ Health Perspect. 2006 Mar; 114(3): A160–A167. doi: 10.1289/ehp.114-a160 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392256/
7. Introduction to Genomics: What’s a Genome?
https://www.genome.gov/About-Genomics/Introduction-to-Genomics
8. Endogenous retroviruses in the human genome sequence. David J Griffiths, Genome Biology volume 2, Article number: reviews1017.1 (2001). https://genomebiology.biomedcentral.com/articles/10.1186/gb-2001-2-6-reviews1017
9. Genome mining shows that retroviruses are pervasively invading vertebrate genomes. Jianhua Wang & Guan-Zhu Han Nature Communications volume 14, Article number: 4968 (2023). https://www.nature.com/articles/s41467-023-40732-w
10. Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs)Tara P Hurst 1 , Gkikas Magiorkinis Viruses 2017 May 31;9(6):130. DOI: 10.3390/v9060130.
11. Mice can inherit learned sensitivity to a smell
By Quinn EastmanDec. 2, 2013 https://news.emory.edu/stories/2013/12/smell_epigenetics_ressler/campus.html
12. STARVATION EFFECTS HANDED DOWN FOR GENERATIONS https://today.duke.edu/2015/07/wormstarvation
13. Cohort profile: the Dutch famine birth cohort (DFBC)— a prospective birth cohort study in the Netherlands. Laura S Bleker,1 Susanne R de Rooij,1 Rebecca C Painter,2 Anita CJ Ravelli,3 and Tessa J Roseboom4. BMJ Open. 2021; 11(3): e042078. Published online 2021 Mar 4. doi: 10.1136/bmjopen-2020-042078. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934722/
14. The Dutch Hunger Winter and the developmental origins of health and disease. Laura C. Schulz. https://www.pnas.org/doi/full/10.1073/pnas.1012911107
15. “Killing Me Softly: The Fetal Origins Hypothesis.”
Almond, Douglas, and Janet Currie. 2011 Journal of Economic Perspectives, 25 (3): 153-72. DOI: 10.1257/jep.25.3.153
https://www.aeaweb.org/articles?id=10.1257/jep.25.3.153
16. Transgenerational genetic effects. Vicki R Nelson1 and Joseph H Nadeau Epigenomics. 2010 Dec; 2(6): 797–806. doi: 10.2217/epi.10.57 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720237/
17. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. John Carstensen, Sören Edvinsson, Tomas Faresjö, et.al. J Med Genet. 2014 Sep; 51(9): 563–572. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157403/
