Post No.: 0589
Fluffystealthkitten says:
Research in epigenetics – which concerns how environmental influences, individual life experiences and age can activate/inhibit the expression of our genes – reveals how our upbringings and lifestyles can influence gene expression, which in turn can alter things like our metabolism or susceptibility to obesity. It’s not just about what genes we have but which particular ones are switched on/off. We now know that ‘genetic’ doesn’t mean ‘un-modifiable’. (Post No.: 0466 also explained how genetic heritability isn’t necessarily fixed.) Geneticists don’t use the term ‘nature versus nurture’ anymore – they prefer ‘nature and nurture’.
Humans may share a lot of DNA with each other and even with other organisms, but a lot of the differences we see depend on which genes are switched on/off. Depending on how the similarities and differences are aggregated, humans may be said to share ~60% of their genes with bananas, but it’s not only about which genes are present but also whether each one is activated/inhibited. All that previously-regarded ‘junk DNA’ isn’t junk after all either but some affects how genes are activated/inhibited. It also shows that gene expression can depend on environmental or lifestyle factors – things that people have some control of.
In epigenetics, the DNA sequence is unchanged but access to the DNA is altered biochemically, which turns the expression of a gene on/off (e.g. a ‘beneficial’ gene off or a ‘harmful’ gene on). Unlike the DNA sequence or genome (evolution) – the epigenome is affected by the environment, upbringing and lifestyle (adaptations). Gene expression can change via DNA methylation or histone acetylation, or by affecting neurotransmission, signal transduction and through activating/inhibiting transcription factors (phosphorylation) around DNA. It’s ultimately about altering which proteins get produced by mRNA, which in turn affect our bodies, and in turn even our thoughts and behaviours – because these are ultimately products of our hormones, neurotransmitters and physical bodies. DNA isn’t laid out straight (unlike how countless textbooks illustrate it) but is all tangled up, and the way it’s tangled up can be like clamping shut the pages of a book so that those pages are inaccessible to read. It’s metaphorically like a computer program with thousands of lines of code but the main program only calls several lines of it. And this expression (particular on/off positions) can also be passed down to children via the germline.
Possibly due to epigenetics, it has been found that children born to women who had gastric bypass surgery are 52% less likely to become obese than their siblings who were born while their mothers were obese. So cutting your own weight down makes a big difference to the chances of your children becoming obese.
Studying the causes and effects of epigenetic mechanisms is incredibly difficult though because unlike the DNA sequence, which is like a written book, we need to also know what happened to the book to ‘clamp some of its pages together’, for which this information won’t be recorded in the book itself. Epigenetic signals are hard to detect in traditional studies with humans. Some human experiments would be deemed too unethical too (e.g. starving a group of children to record the epigenetic effects).
But via fluffy mice studies, scientists have found that turning off the agouti gene can turn fat yellow mice into skinny brown mice – they have the same genes but look completely different. The skinnier brown mice were also less susceptible to cancer and diabetes and thus lived longer. Scientists changed a generation of fat yellow mice into skinny brown mice by feeding the pregnant mother mice with a diet high in methyl donors (which can be found in e.g. onions, garlic and beets, and in food supplements like folic acid).
What we don’t yet know though, is how methylation (or the lack of) affects different people, whether one action will have unforeseen side effects, and how different environmental factors might interact with each other to interfere with these processes? It’s all incredibly complex – a slight change or introduction of a new variable can dramatically change the end result. We know in principle that epigenetic effects are happening, but it may take a while before we can say with great confidence specifically which environmental causes cause what effects in humans.
When, as well as which, genes are expressed (e.g. during an embryo’s development in the womb as the early cells are just first dividing) can matter. Generally, the earlier the causes, the greater the effects over time. Therefore complications during pregnancy or when giving birth can affect a child most greatly. Well we already knew that a mother’s choice to smoke, drink alcohol or abuse other recreational drugs during pregnancy can adversely affect her offspring. Apparently, even whether your mother ate green leafy vegetables or not when you were in the womb could’ve had a bearing on your likely lifespan via epigenetics. Which parent you receive a disease allele from (imprinting) makes a difference concerning the expression of some diseases or disorders too (e.g. Prader-Willi versus Angelman syndrome). Sometimes, if it comes from one parent it can be harmful while from the other it can be protective!
Prenatally and just before puberty are two key periods when our epigenomes are highly susceptible to disruption by external factors such as toxins, smoking, alcohol and drugs – these will affect you later in life, as well as your offspring potentially, in terms of the diseases you, and they, may get. It could therefore affect the trajectory of your children’s lives, and of those of their children too.
Transgenerational epigenetic inheritance is the theory that environmental factors (e.g. diet, lifestyle choices and behaviours, and stress) can change the health, not only of the people who are exposed to them – but also their descendants epigenetically (i.e. non-DNA heritable changes). Experts believe that the environmental conditions and life experiences of parents, grandparents, and possibly even great-grandparents, can change the epigenomes of egg and sperm cells, and the epigenomes of developing foetuses in pregnant women, thus effectively changing the genetic code of their offspring and descendants multiple generations down the line.
Through this mechanism, new phenotypic traits can appear within a single generation, and be passed onto kids, grandkids, and possibly beyond. So our lifestyles – not just our genes – can have a major effect on our future grandchildren. For example, some early evidence suggests that smoking and overeating can cause genes related to obesity risk to become ‘switched on’ while genes carrying messages for longevity to become ‘switched off’. This means that, in addition to the personal harm that can arise from overeating or smoking, these lifestyle choices may predispose one’s descendants to disease and premature death too. The Dutch Hongerwinter affected many generations afterwards, and this was purportedly due to epigenetics. Our life experiences therefore affect our children via foetal programming (e.g. if we over or under-nourish ourselves, smoke or stress out).
In the past, the understanding of diseases, like diabetes, focused on the interaction between the genes we inherit through a long lineage along with the environment – but the concept of epigenetics has shed new light on how changes can occur within much shorter timescales.
All this seems to support the role of parental lifestyles and parenting styles on affecting the health of children, grandchildren and beyond in a way that’s deeper than just through teaching behavioural habits directly or via imitation. It reinforces the responsibilities of parents regarding the health of their children. We affect our children’s health in deeper ways than we may have thought. What we do before a child is even first conscious, or conceived, can have a huge and far-ranging effect on the rest of their life. Early intervention is therefore key and is for the sake of every innocent child who enters this world – not for things like getting ahead in academic terms but getting used to flavours and handling stress, for example. (Of course, parents could in turn blame their own parents for the epigenomes they inherited and so forth, but we won’t go there today(!)) Parents may not be able to undo the genetic ‘on/off switch’ changes they have already passed onto the kids they’ve already had – but encouraging a healthier family lifestyle now will still be invaluable to their and their children’s health. And epigenetics doesn’t just apply to passing on potentially negative traits or health risks but also the benefits of inheriting healthy or protective factors.
Does this mean that we’re all fated to our destinies because our own trajectories were shaped by our parents, grandparents and even beyond? Not completely. It may mean that some of us will need to be more careful in life than others as to what environmental stressors we’re exposed to, but there’s still plenty of personal control of one’s own destiny – if you change your environment and lifestyle then you’ll in some way reorient the trajectory for yourself (and for your own offspring too). ‘Increased risk’ is not fate unless something has 100% certainty. And if negative traits can appear within a single generation then positive traits can appear within a single generation too (e.g. with you). 50-year-old twins can exhibit over three times the epigenetic differences compared to each other than 3-year-old twins compared to each other – suggesting that even for twins, as they grow up and therefore experience ever more diverging lifestyles from their siblings, their different environments are still changing them in meaningful ways. Meow.
Exercise can temporarily change our own epigenomes to allow us to burn off more energy for a few hours during and after exercise. So if you’re disappointed with what genes you were born with – change how they’re switched on/off by changing your lifestyle! Going on regular crash diets, meanwhile, won’t only slow down your own immediate metabolism but may also alter gene switching so that you (and your future offspring) will more easily retain fat and energy.
Cancers could potentially be triggered by epigenetics – after all, they’re at least partially triggered by environmental factors such as smoking (and methylation may be the precise mechanism how?) Regularly consuming cooked turmeric (curcumin) may switch genes related to reducing the risk of cancers and other diseases. Scientists are beginning to deliberately exploit the concept of epigenetics as a strategy for developing new approaches to tackling diseases with genetic roots – drugs are already being produced that act by switching off ‘faulty’ genes in an epigenetic fashion. This type of genetic approach could be a valuable one in the fight to prevent, treat or cure a number of conditions such as cancer, diabetes and Alzheimer’s disease.
We’re only really just beginning to study the effects of synthetic chemicals in the human body. In the future, setting standards for chemical safety may also need to account for any potential epigenetic effects too.
…Some of the conclusions of the specific studies relied upon for this post are tentative as more research and replication is being done, but we do know for sure that it’s not just about what genes we’re born with but how they’re switched on/off. Our phenotypes are affected partly by our diet, activities and environment. We’ve long known it’s about the combination of genes and environment, and epigenetics doesn’t change that – it actually advances the understanding of one way that they complexly interact with each other. And so ultimately, the advice for parents hasn’t changed – they need to live healthily and lead by a healthy example. Mothers-to-be need to live healthily. I suppose this research also shows how fathers-to-be need to live healthily too because epigenetic signals can be passed through the sperm cells, which are constantly being produced anew; unlike egg cells, although women can pass epigenetic changes to children in utero. We all need to live healthy lifestyles for our own sakes too. Lifestyles that are too sedentary aren’t good. We can’t always unilaterally change our environments though (e.g. an environment with too many processed food temptations targeted at children), hence governments have their responsibilities too.
Meow.
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