What's the reason for the decline in immunity when you're older? Genome Biology。

Title: Genome organization and chromatin analysiss, contentional downregulation of insulin-like growth factor signaling as a hallmark ofaging in developmenting B cells
Journal:
Hashem Koohy†, Daniel J. Bolland†, Louise S. Matheson†, Stefan Schoenfelder, Claudia Stellato, Andrew Dimond, Csilla Várnai, Peter Chovanec, Tamara Chessa, Jeremy Denizot, Raquel Manzano Garcia, Steven W. Wingett, Paula Freire-Pritchett, Takashi Nagano, Phillip Hawkins, Len Stephens, Sarah Elderkin, Mikhail Spivakov, Peter Fraser, Anne E. Corcoran and Patrick D. Varga-Weisz
Published: 2018/09/05
Digital Identification Number: 10.1186/s13059-018-1489-y
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Why is our immune system getting worse with age? A new mouse model study published on
explores the hypothesis that changes in gene regulation in specialized immune cells, or pregenesomes of B cells, cause these cells to decrease with age as we age. The study found that aging can affect several genes involved in growth and proliferation-related path paths, which is an important step in understanding aging and the immune system.life expectancy has doubled over the past few centuries as a result of improved health care, nutrition and living conditions. In 1841, a baby girl was born to be 42 years old, while in 2016 she was expected to live to 83. People live longer and older people are healthier than in the past.
, the increase in healthy life expectancy has not kept pace with the increase in life expectancy. The ageing of the population poses serious economic, health and social problems. To solve these problems, we need to understand the aging process and use this knowledge to ensure a healthy aging and a happier and healthier old age.
as we get older, the tissues of the body get older in different ways. For example, when Patrick (the male author of this article) turned 40, his hair began to turn gray (and Anne (the female author of this article) didn't change at all), and when both were in their 50s (recently!). ), the old flower mirror has become a necessity.in the immune system, thymus degeneration (shrinking) from puberty may be the first step in aging. Other general declines in the immune system occur long after they begin. In fact, some people even think that "age" may be a form of obtained immunodeficiency.
has now been determined that older persons are more vulnerable to infections such as pneumonia and have a weak immune response. This susceptivity indicates that the immune system has lost its ability to obtain immunity, which produces antibodies that are necessary to fight many infections.
antibodies are produced by B cells and are produced in very complex ways, involving many prescellular cell types. All the early steps of the process occur in the bone marrow, where pregeneral B cells are produced from stem cells that make blood (to produce blood).
the process of growing older strongly affects these early steps, reducing the number of pregenerant B cells and the development of mature B cells in which these cells secrete antibodies. Importantly, this reduces the diversity of antibody libraries.
because each B cell produces different antibodies, this in itself is like a numbers game:We don't yet know what causes the number of these prescellular cells to decrease with age. One theory is that this is related to the effects of genes on the aging process. Many genes encode proteins, which are also tools used by cells to function. Other genes encode regulatory molecules that control these proteins. The way genes are packaged and organized in the nuclea has important effects on their expression, for example, on or off.
to test this theory, we decided to explore whether changes in gene expression devices and genomic tissue in B-cell pregenes could lead to this decline. Because it is difficult to obtain human bone marrow under experimental conditions, we conducted these studies in mice with closely related to the human immune system.
With the efforts of several research groups at the Babraham Institute, including the laboratories of Peter Fraser, Mikhail Spivakov, Patrick Varga-Weisz, Sarah Elderkin and Anne Corcoran, we have for the first time conducted a comprehensive study of how aging affects gene expression through genomic regulation of bone marrow B-cell pregeners in mice.
comparing gene expression in B-cell pregenesomes from young and old mice, we found that aging affects only a relatively narrow set of genomes. It is worth noting that some genes in these genes, which include long non-protein-coded transcripts and small regulatory transcripts called tiny RNA, are involved in pathlines that respond to nutritional status and are associated with growth and proliferation.
particularly,
identified changes in genomic tissue associated with this reduction.
our study suggests that repositioning genes between active and inhibitory nuclear environments can lead to changes in gene expression as they age. This is an unusual way to downgrade, as signaling paths are usually regulated by fine-tuning of cytostic events such as phosphate.
It's worth noting that some ground-breaking studies in the past have shown that the absence or mutation of components in the IGF path path line can extend the lifespan of several model organisms, such as worms, fruit flies, and mice, and genetic studies have found some evidence in human beings.
there may be a number of reasons for this, including reduced susceptivity to external stress due to reduced metabolism or cell proliferation. As far as we know, the survival of B cells in older mice is the first example of "natural" reduction of this path.
some breakthroughs in our findings, there are still many unresolved issues. Future studies should shed light on the extent to which the changes we observe are inherent in B-cell pregenerals, or depending on the changed environment in which these cells are located, as they age. In addition, we need to understand whether these changes contribute to cell resilience or negatively affect their function.
interesting question for future research is whether these regulatory mechanisms affect other tissues and systems in the aging process. 。 Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. 。 Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. 。 Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors. 。 (
, 13.2 -
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)publishes outstanding research in all areas of biology and biomedicine studied from a genomic and post-genomic perspective.
The current impact factor is 13.214* and the journal is ranked 4th among research journals in the Genetics and Heredity category by Thomson Reuters. Genome Biology is the highest ranked open access journal in the category.
(Source: Science.com)