epigeneticsMeaning “above genetics”, resulting from changes without involving changes in the way a person’s genes function. dna Self. For example, by adding molecules called methyl groups to DNA – a process called DNA methylation – epigenetics can turn genes on or off, or increase or decrease their activity.
Environmental factors – e.g. Tension, Diet And smoking – Can promote epigenetic modifications which in turn can lead to such conditions colorectal cancer And heart disease.
But some of these epigenetic modifications can be reversed. This means that epigenetics may reveal potentially new and targeted ways to modify disease risk, Alika Maunakeaa professor of anatomy, biochemistry and physiology at the University of Hawaii at Manoa told Live Science.
Growing up on a subsistence farm in Hawaii, Maunakea said she learned from a young age that the environment plays a major role in shaping the health of a community.
Now, Maunakea has been researching epigenetics for more than 20 years and heads the Maunakea LabWhich focuses on how environmental and epigenetic factors act at the molecular level to increase health disparities. Live Science spoke with Maunakea about how epigenetics affects health and what her research is uncovering about how epigenetics plays a role in exacerbating health disparities among Native Hawaiians.
Sophie Bardugo: Can you explain how genetics and epigenetics interact in a health context?
Alika Mounakiya: This is a bit complicated because there is a lot of nuance and variability in understanding the context behind it. Disease risk is determined not only by genetic predisposition but also by environmental factors and lifestyleand even Things Our Grandparents Experienced. This is where epigenetics comes in.
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Epigenetics is this intermediate state between the environment and the genome, and it helps to regulate the genome. Therefore, even if you have a genetic risk, it does not mean that the risk will be increased.
Professor Alika Maunakea heads the Maunakea Lab at the University of Hawaii at Manoa.
(Image credit: OZY Magazine)
They [genetics and epigenetics] are related to each other because there are certain regions in the genome where if a polymorphism – a change – occurs in the sequence, it can sometimes lead to a change in epigenetic patterning. So there is this interconnected relationship between the two. In some cases, it is difficult to completely separate the genetic variability that is conferring the risk of a particular outcome and the epigenetic variability that is contributing to that same risk.
If there’s a lot of epigenetic variability, rather than genetic variability, that’s contributing to that risk – then it’s likely that there are lifestyle changes, things that you can modify at an individual level to reshape the epigenome, that will help reduce that risk. So there’s still a lot of work left [to be done] Understanding that relationship can and will require a multidisciplinary approach and integrating multiple types of data.
SB: What got you interested in this field?
AM: My great-grandmother was a Hawaiian healer – what we call “kahuna la‘u lapa‘u” – and she taught me “na mea Hawaii,” so “all things Hawaiian.” There was a deeper understanding and recognition of how maintaining a healthy built and natural environment around us truly shapes our health and well-being.
I was really interested in understanding why our population, Native Hawaiians, has a higher prevalence of specific chronic conditions that we never had before Westernization, and trying to understand why we see it earlier, at a younger age, in our population than other populations? That was something that really bothered me. I wanted to understand it more at the cell and gene level, so I think I naturally gravitated toward epigenetics because I think it explains that phenomenon.
My main goal is to really apply that information in a more clinical, community-based setting where that information can be used to enable tools and approaches that will help reduce the onset of these disorders in our community.
What we are now learning is that epigenetic processes may, in fact, occur before disease symptoms. We can actually identify some early indicators of disease trajectory before its clinical diagnosis, using epigenetic analyses. Trying to understand how this might play a role in enabling prevention is a big thing in my lab right now.
SB: What health conditions do you look at in your research?
AM: One of the situations we are considering is type 2 diabetesin which it is High prevalence among Native Hawaiians. This is three times higher than the state’s other populations, and also has an earlier onset of the disorder: Hawaiians are diagnosed with type 2 diabetes about 10 to 15 years younger than other populations in the state. [They also have] Type 2 diabetes has a high mortality rate and other chronic conditions.
pre-colonization [pre-Western contact in 1778]we never had [chronic conditions like type 2 diabetes] As an issue in our population. Our “Kahuna La’u Lapa’u” [Hawaiian healer]Like my great-grandmother, she had to invent new words for them based on the phenotype [how the condition is presenting]. so we call it [type 2 diabetes] “Mimi Koko,” meaning “sweet blood.”
The first documented arrival of Europeans to the Hawaiian Islands in 1778 led to significant changes in diet and lifestyle and the emergence of new diseases that devastated local communities.
(Image credit: Michael Nicholson/Contributor via Getty Images)
It’s not clear how much of our genotype is actually related to the risk of that disease, but we think that environmental factors and the changes that have occurred since colonization and Westernization, and changes in our lifestyles and our societies – decolonization and especially displacement – have really led us to a situation where there is now a higher incidence of these conditions. And so we’re trying to understand what, at the molecular level, is shaping those outcomes and how we can use that information to prevent it from happening in the first place.
One question that really came up immediately was what exactly is behind the early age of onset? Why is its prevalence not only higher here, but why is it happening at a younger age? That question still remains to be clarified, but we believe that some symptoms, e.g. obesityModify that risk.
To get to that question, we really need to understand at the molecular level, are there any disruptions in the aging process in this population? Are there differences in susceptibility to aging in this population compared to other populations that may be affected by these environmental factors?
There is an event called “epigenetic aging,” Who Steve Horvath published a paper early in 2013And identified that there are certain sites in the genome that are epigenetically regulated – particularly by DNA methylation – that correlate really well with chronological age in a healthy population.
But there were also some individuals who demonstrated what we would call outliers in this relationship, where there were cases where individuals appeared to be Higher estimated epigenetic age than their chronological age. then they will appear [to be] Biologically they are aging faster than normal. And then there were people at the opposite end, where their estimated epigenetic age actually appeared to be younger than their chronological age. and we think so generally corresponds to health.
We found something similar in the Native Hawaiian population: Native Hawaiian populations have a higher frequency of individuals who appear, at the molecular level, They are aging faster than other populationsSuch as the white population and the Japanese American population in the state of Hawaii.
And we know that this matches the higher prevalence of these chronic conditions that we see, like diabetes, in Native Hawaiians compared to these other populations, as well as some of these risk factors, like obesity. And we’ve seen it in our community. People who live in socio-economically poor areas are more likely to live longer.
Research shows that more Native Hawaiians have faster rates of epigenetic aging than other populations in the state of Hawaii.
(Image credit: Kroot Studio via Getty Images)
We’re learning that there are some individual-level lifestyle factors that can actually potentially modify this. [epigenetic] risk. We have identified that even among Native Hawaiians living in socioeconomically poor areas, at the individual level, if there are high levels of physical activity as well as education – and even, in some cases, nutrition – then those individuals, even within that population, tend to have normal biological aging.
And what we learned from this is that individuals who experience accelerated aging have a higher risk of diseases like diabetes, but that risk can potentially be modified by making healthy lifestyle changes.
Now we’re seeing not only that there is that disparity and potentially a mechanism that may underlie that disparity, but also potentially some clues as to what kinds of environmental factors may shape that molecular process.
we have one pilot study We published a few years ago that Native Hawaiians who have diabetes, when they do a lifestyle intervention that specifically involves social support, they not only improve their glycemic control – which is really the main purpose of this intervention – through this lifestyle modification over a 12-week period, but we also showed that the cells that are related SwellingThe behavior of those cells is actually modified by that intervention, and they actually seem to be less inflamed. [Glycemic control is the management of blood glucose levels.]
The epigenome of those cells is also being modified in a pattern that is similar to non-diabetic conditions.
So we think that those cells play a role in the pathology and etiology [cause] of disease and metabolism Dysregulation in individuals with diabetes. But we also think that modulating their inflammatory status may actually help improve glycemic control. So we’re trying to understand how much epigenetic patterning might have to do with it [inflammation].
We’re finding very clear relationships that indicate that potentially we can also use that information to identify more effective interventions that can actually target this [epigenetic] Process, where we can reduce the inflammatory status of these individuals at the cellular and molecular level.
We’re really hoping that this could be useful for prevention, because we can identify these before clinical diagnosis. [Editor’s note: These findings have not been published in a peer-reviewed journal.] And we think that if we can do that at the individual level, particularly in high-risk populations, we can recommend appropriate interventions – or adapt interventions that exist – to target changes in the epigenome that then impact the physiology and outcomes of the condition. So that’s something that we’re trying to develop further.
SB: How resource-intensive is it to observe a person’s epidemiology?
AM: Unfortunately, it is resource-heavy at this stage. So I think it will take time to develop new technologies and tools that are more targeted and can be used in a more clinical setting.
But genome sequencing is becoming more cost-effective than before and the lower costs it is now moving towards increase the feasibility of adopting some of these approaches.
Editor’s note: This interview has been condensed and edited for clarity.