{"id":9621,"date":"2017-03-31T09:51:43","date_gmt":"2017-03-31T07:51:43","guid":{"rendered":"https:\/\/news.embl.de\/?p=9621"},"modified":"2024-03-22T13:39:34","modified_gmt":"2024-03-22T12:39:34","slug":"1703-ageing-cell-coordination-breakdown","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1703-ageing-cell-coordination-breakdown\/","title":{"rendered":"Ageing: cell coordination breakdown"},"content":{"rendered":"\n

Researchers from the European Bioinformatics Institute<\/a> (EMBL-EBI), University of Cambridge, the Wellcome Trust Sanger Institute and the Cancer Research UK\u2013Cambridge Institute (CRUK-CI) have shed light on a long-standing debate about ageing and why the immune system weakens with age. Their findings, published in Science<\/em>, show that immune cells in older tissues lack coordination. These cells also exhibit more variability in gene expression compared with their younger counterparts.<\/p>\n\n\n\n

Settling the debate<\/h2>\n\n\n\n

We\u2019ve all witnessed the progressive decline of function that comes with ageing. But what exactly causes this decline? And why does it happen at different rates for different parts of the body? To find answers, scientists need to unpick the mechanisms of ageing at the molecular level, for every tissue. Today\u2019s study focused on immune tissue: specifically, CD4+ T cells.<\/p>\n\n\n\n

The immune system is like a symphony orchestra, with different types and subtypes of cells working together to fight infections. But as the immune system ages, its response to infection weakens for reasons that are not yet clear. One long-standing debate amongst scientists concerns two central hypotheses. Either the functional degradation is caused by a loss of cellular performance, or it is down to a loss of coordination among cells.<\/p>\n\n\n\n

single-cell sequencing allows researchers to individually look at thousands of genes at any given time<\/p><\/blockquote>\n\n\n\n

To resolve the debate, scientists have studied many different cell types, analysing \u2018average\u2019 gene expression profiles. Today\u2019s study employed high-resolution single-cell sequencing technology to create new insights into how cell-to-cell variability is linked with ageing. The researchers sequenced the RNA of na\u00efve and memory CD4+ T cells in young and old mice, in both stimulated and unstimulated states.<\/p>\n\n\n\n

Their findings clearly showed that loss of coordination is a key component of the impaired immune performance caused by T cell ageing.<\/p>\n\n\n\n

The DNA smoothie<\/h2>\n\n\n\n

\u201cYou could think of DNA sequencing as a fruit smoothie,\u201d explains John Marioni, Group Leader<\/a> at EMBL-EBI and at CRUK-CI. \u201cTraditional sequencing technology is like taking a sip of the smoothie, then trying to guess the ingredients. Single-cell genomics now lets us study the ingredients individually. This way, we get direct insight into the constituent parts. Extrapolating, this means that single-cell sequencing allows researchers to individually look at thousands of genes at any given time.\u201d<\/p>\n\n\n\n

A phalanx of immune cells<\/h2>\n\n\n\n

Duncan Odom, Group Leader<\/a> at the University of Cambridge\u2019s Cancer Research UK Cambridge Institute and associate faculty at the Wellcome Trust Sanger Institute, shares a further analogy to explain how immune cells fight infection.<\/p>\n\n\n\n

\u201cImagine the immune system as a \u2018cell army,\u2019 ready to protect the body from infection,\u201d says Odom. \u201cOur research revealed that this army is well coordinated in young animals. All the cells work together and operate like a Greek phalanx to block the infection.\u201d<\/p>\n\n\n\n

Odom goes on to explain that this tight coordination makes the immune system stronger. It also allows the immune system to fight infection more effectively. The team\u2019s study shows that as the animal gets older, cell coordination breaks down.<\/p>\n\n\n\n

\u201cAlthough individual cells might still be strong, the lack of coordination makes their collective effectiveness lower,\u201d Odom concludes.<\/p>\n\n\n\n

Ageing – older and more variable<\/h2>\n\n\n\n

Previous studies have shown that in young animals, immunological activation results in tightly regulated gene expression. This study further reveals that activation results in a decrease in cell-to-cell variability. Ageing increased the heterogeneity of gene expression in populations of two mice species, as well as in different types of immune cells. This suggests that increased cell-to-cell transcriptional variability may be a hallmark of ageing across most mammalian tissues.<\/p>\n\n\n\n

All the cells work together and operate like a Greek phalanx to block the infection<\/p><\/blockquote>\n\n\n\n

\u201cThere is a great deal of interest in how biological ageing happens, we don’t know a lot about molecular ageing,\u201d says Celia Pilar Martinez-Jimenez<\/a>, experimental lead and Postdoctoral Fellow at the Sanger Institute and CRUK-CI. \u201cThis research initiative explored a new facet of cell response to disease, while also tackling questions related to ageing.\u201d<\/p>\n\n\n\n

Nils Eling<\/a>, computational lead of the project and PhD student at EMBL-EBI and CRUK-CI highlights that \u201cthe advantage of analysing gene expression from single cells is to detect how cell populations synchronise their response. It is interesting to see that ageing strongly distorts this response \u2013 a phenomenon which could not be observed before.\u201d<\/p>\n\n\n\n

The interdisciplinary study paves the way for a more in-depth exploration of the mechanisms by which different types of cells age. It also illustrates the potential of single-cell sequencing to enable a richer understanding of cell development and activity.<\/p>\n\n\n\n

This post was originally published on EMBL-EBI News.<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers use single-cell sequencing to understand how cells age<\/p>\n","protected":false},"author":47,"featured_media":9626,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[28,36,41,330,491],"embl_taxonomy":[],"class_list":["post-9621","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-bioinformatics","tag-embl-ebi","tag-genetics","tag-malaria","tag-single-cell-genomics"],"acf":{"article_intro":"

Researchers use single-cell sequencing to understand how cells age<\/p>\n","related_links":false,"article_sources":[{"source_description":"

Martinez-Jimenez C P et al.<\/em> Science<\/em>, published in print and online 31 March 2017. DOI: 10.1126\/science.aah4115<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1126\/science.aah4115"}],"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"\nAgeing: cell coordination breakdown \u2013 EMBL<\/title>\n<meta name=\"description\" content=\"Researchers from the European Bioinformatics Institute (EMBL-EBI) and the University of Cambridge have used single-cell sequencing to understand ageing.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science\/1703-ageing-cell-coordination-breakdown\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Ageing: cell coordination breakdown \u2013 EMBL\" \/>\n<meta property=\"og:description\" content=\"Researchers from the European Bioinformatics Institute (EMBL-EBI) 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