Introduction: The recently popular “Sanhua Evaporated Milk” and “Hikes Black Technology “It has triggered food safety anxiety among many people, concerned about the risks to their health. In fact, genes, environment and age all play important roles in our health, but which one is the most important? Many people smoke and drink all their lives, but they are still healthy and live a long life; many people are careful and take care of themselves early, but they cannot escape the disease. In fact, the essence of these phenomena still needs to be found in genes.
The relationship between age and health varies from person to person. In the case of successive U.S. presidents, Ronald Reagan developed Alzheimer’s disease in his 80s and died from complications of the disease at 93; Franklin Roosevelt died of a cerebral hemorrhage at the age of 63; Jimmy Carter, the oldest living president in U.S. history, suffered from cancer at the age of 95 and is still alive at the age of 98 (Figure 1 ). Beyond age, the environment also affects health. Even identical twins with identical genomes have differences in gene expression with age, implying that the environment modulates gene expression.
Figure 1 Ronald Reagan, Franklin Roosevelt and Jimmy Carter (Source: Wikipedia)
In fact, as we age, gene expression levels change and many biological processes deteriorate, leading to cell dysfunction and worsening tissue activity. Medawar’s theory of germline mutation accumulation states that because older individuals are less likely to contribute their genetic information to the next generation, late-onset mutations accumulate much faster than early-onset mutations. In this case, natural selection is weaker and cannot consistently eliminate these mutations. Over time, these harmful late-onset mutations will accumulate and lead to aging. However, how to quantify the tissue-specific effects of increasing age and genetics on gene expression patterns is inconclusive.
On October 3, 2022, a research team from the University of California, Berkeley published a research result entitled “Tissue-specific impacts of aging and genetics on gene expression patterns in humans” in Nature Communications (Fig. 2) [1]. Research shows age plays a more important role than heredity in determining which genes are expressed in our bodies and affects susceptibility to disease.
Figure 2 Research results (Source: [1])
This study established a statistical model to assess the relative roles of genetics and aging in 27 different human tissues from 948 individuals and systematically assessed the effects of genetics, aging, and environment on approximately The relative impact of 20,000 human gene expression patterns.
Findings:
01
Gene expression prediction: little effect in old age
Human genetic makeup can help predict gene expression in younger years, but it is less useful in predicting which genes will increase or decrease in old age. Age affects the predictive power of expression Quantitative Trait Loci (eQTL), but to varying degrees in different tissues and in older and younger individuals: younger individuals are significantly better than older individuals for genotype expression prediction.
02
Gene expression is influenced by the environment: increases with age
Traits are determined by a combination of genetic and environmental factors. The concept of “heritability” refers to the proportion of a trait that is genetically regulated. The higher the heritability, the greater the proportion of genetic factors and the smaller the proportion of environmental factors in the determination of traits. Gene expression heterogeneity differs between young and old in many tissues. The increased expression differences reduced the average heritability of gene expression in these tissues, both in the elderly and in the young.
03
Age-influenced tissue aging: cancer-prone tissue limits life
The average heritability of gene expression was largely consistent across tissues. While the expression of many individual genes is strongly influenced by genetics, genetics explains a small fraction of overall gene expression. In contrast, age contributed on average 20-fold more than genetics to changes in gene expression in tissues. The coordinated decline of mitochondrial genes and translation factors is a ubiquitous phenomenon of aging across multiple tissues, with potential phenotypic consequences.
Age-related gene expression patterns were more tissue-specific than genetically influenced gene expression patterns, and were found in five tissues (blood, colon, arteries, esophagus, fat ), age has a much stronger role than genetics in driving gene expression patterns. These five tissues happen to be the ones that change throughout a human life and are the ones that generate the most cancers. Every time these organizations renew themselves, it is possible to produceGene mutations that cause disease. In the later years of human beings, these genes are easily affected by somatic mutations and exist in a cancerous manner, limiting the normal operation of the body and limiting the development of life.
This study finds that aging and the environment are far more important than genetic variation in influencing gene expression in humans; genes with eQTL tend to be more affected than genes with age-related gene expression patterns Fewer evolutionary constraints and therefore less potential biological importance. The insights provided by this study on tissue-specific aging patterns and the relative effects of genetics and aging on gene expression will facilitate future studies of gene expression, chromatin structure and epigenetics across tissues and cells. Elucidating how programmed and stochastic processes of aging drive human disease.
Corresponding author Peter H. Sudmant (Figure 3) said: “Scientists have done a lot of work in human genetics to understand how human genetic variation regulates genes. Our project is to address this Question: How does age affect gene expression? We found that genetics actually becomes less important as we age. These findings have important implications for research linking diseases of aging to genetic variation in humans : Such studies should perhaps pay less attention to genetic variants that affect gene expression in pursuit of drug targets. Almost all common human diseases are diseases of aging, such as Alzheimer’s disease, cancer, heart disease , diabetes, etc., and the prevalence of these diseases increases with age. A large number of public resources have been used to identify genetic variants that predispose to these diseases. In fact, as we age, genetics influences gene expression The effect will be smaller and smaller. Perhaps, as we try to determine the cause of these diseases of aging, we need to be aware of that.”
Figure 3 Peter H. Sudmant (Source: University of California website)
On the main factors affecting gene expression, Sudmant said: “Environment accounts for one-third of the age-dependent changes in gene expression. The air we breathe, the water we drink, the food we eat , as well as our level of physical activity are environmental factors.We all age in different ways, but gene expression in older adults is less stable. Genetics are roughly equally important in all tissues, but aging varies widely across tissues, with age playing a much stronger role than genetics in driving gene expression patterns. From evolution Some super-conserved, very important genes have to be activated later in life. In fact, this is problematic because it means that these genes are susceptible to somatic mutations and become cancerous in a way that Always active. So, it limits our ability to continue living and implies the limits of our evolution.”
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References:
[1]Yamamoto R, Chung R, Vazquez JM, et al. Tissue-specific impacts of aging and genetics on gene expression patterns in humans. Nat Commun. 2022 Oct 3;13(1 ): 5803. doi: 10.1038/s41467-022-33509-0. PMID: 36192477; PMCID: PMC9530233.
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