Overview: Age itself plays a larger role than genetics in age-associated gene expression and susceptibility to certain diseases.
sauce: University of California, Berkeley
While there is much speculation and research about how our genetics influence how we age, a study from the University of California, Berkeley found that individual differences in DNA become less important as we age. , have been shown to be more susceptible to age-related diseases such as diabetes and cancer. .
In a study of the relative effects of genetics, aging, and the environment on the way approximately 20,000 human genes are expressed, researchers found that aging and the environment influence the expression profile of many of our genes through genetic variants. I have found that it is much more important than old.
The level at which a gene is expressed, or ratcheted up or down in activity, determines everything from hormone levels and metabolism to the recruitment of enzymes that repair the body.
“Your genetics — what you got from your sperm and egg donor and your evolutionary history — depends on who you are, your phenotype such as height, weight, whether you have heart disease, how you Will it affect me?” said Peter Sudmant, assistant professor of integrative biology at the University of California, Berkeley, and member of the campus’s Center for Computational Biology.
“In human genetics, a tremendous amount of research has been done to understand how genes are turned on and off by genetic variation in humans. It was born from the question, “How is it affected by an individual’s age?” And the first result we found was that your genetics don’t actually matter as you get older.
In other words, an individual’s genetic makeup is useful in predicting gene expression when young, but less useful in predicting which genes will increase or decrease as one ages. For this study, we are over the age of 55.
For example, identical twins have the same set of genes but differ in gene expression profiles as they age. This means that twins can be very different ages from each other.
The findings will have implications for efforts to link age-related diseases with genetic variations in humans, Sudmant said. Such studies should probably focus less on genetic variants that affect gene expression in pursuing drug targets.
“Almost all common human diseases, such as Alzheimer’s, cancer, heart disease and diabetes, are diseases of aging. All these diseases increase in prevalence with age,” he said. .
“Vast amounts of public resources are being spent on identifying genetic variants that predispose to these diseases. It’s just that it’s less important for gene expression. So perhaps we should keep that in mind when trying to identify the cause of these aging diseases.
Sudmant and his colleagues reported the results to the journal this week. Nature Communications.
Medawah’s hypothesis
The findings are consistent with Medawah’s hypothesis. Genes that are turned on when young are more constrained by evolution because they are important for reproductive survival, whereas genes that are expressed after reaching reproductive age are under no evolutionary pressure. Therefore, we would expect even more variation in how genes are expressed later in life.
“We all age in different ways,” says Sudmant. “Young individuals are closer together in terms of gene expression patterns, while older individuals are further apart. It’s like the flow of time as gene expression patterns become more and more irregular.”
This study is the first to look at both aging and gene expression in such a wide variety of tissues and individuals, Sudmant said. He and his colleagues built a statistical model to assess the relative role of genetics and aging in 27 different human tissues obtained from approximately 1,000 individuals, and found that the effects of aging were different for different tissues. I have found that there is more than double the difference.
“In every tissue in the body, genetics is about as important. It doesn’t seem to play more roles in one tissue or another,” he said.
“However, aging is highly tissue-dependent. Age plays a much stronger role than genetics in driving gene expression patterns in blood, colon, arteries, esophagus, and adipose tissue.
Sudmant and colleagues also found that Medawar’s hypothesis does not hold for all organizations. Surprisingly, in five tissue types, evolutionarily important genes were expressed at higher levels in older individuals.
“From an evolutionary perspective, until we look closely at these tissues, it’s counterintuitive that these genes are active,” Sudmant said.
These five tissues happen to be the ones that are constantly being replaced throughout our lifetime and are also the ones that give rise to the most cancers. Every time these tissues are replaced, there is a risk of genetic mutations that can lead to disease.
“I think this tells us a little bit about the limits of evolution,” he said. “For example, your blood must constantly multiply in order for you to live, so these highly conserved and very important genes must be activated later in life.
“This is a problem because it means that these genes are prone to somatic mutations and will be turned on forever in a bad cancer-like way. It gives us a little perspective on the
Sudmant pointed out that the study indirectly shows the effects of the environment on aging. This is all effects other than age and genetics. It includes not only the air you breathe, the water you drink and the food you eat, but also your level of physical exertion. Environment accounts for up to one-third of age-related changes in gene expression.
See also
Sudmant performed similar analyzes of genes expressed in several other organisms (bats and mice) to see how they differed and whether the differences were related to the different life spans of these animals. Checking it up.
Ryo Yamamoto and Ryan Zhang, graduate students at the University of California, Berkeley, are co-first authors of the paper. Other co-authors are Juan Manuel Vazquez, Huanjie Sheng, Philippa Steinberg, and Nilah Ioannidis.
Funding: This work was supported by the National Institute of General Medical Sciences (R35GM142916) at the National Institutes of Health.
About this aging and genetic research news
author: robert sanders
sauce: University of California, Berkeley
contact: Robert Sanders – University of California, Berkeley
image: Image credits UC Berkeley
Original research: open access.
“Tissue-specific effects of aging and genetics on human gene expression patternsBy Peter Sudmant et al. Nature Communications
Overview
Tissue-specific effects of aging and genetics on human gene expression patterns
Age is a major risk factor for many common human diseases. Here we quantify the relative contributions of genetics and aging to gene expression patterns across her 27 tissues in 948 humans.
We show that the predictive power of quantitative trait loci of expression is affected by age in many tissues. By jointly modeling the contributions of age and genetics to variations in transcript levels, we found the heritability of expression (time2) is consistent across tissues, but the aging contribution differs by more than 20-fold in the five tissues, R2age>h2Rage2>h2.
Although the power to purify selection is stronger in genes expressed later in life than in early life (Medawar’s hypothesis), some highly proliferative tissues were found to exhibit the opposite pattern.
These non-medawarian tissues show a high rate of cancer and age-related somatic mutations of onset. In contrast, genes under genetic control are less constrained.
Together, they demonstrate a distinct role for aging and genetics on expression phenotypes.
