Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging

Abstract Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hwang-Yeol Lee, Yeonsu Jeon, Yeon Kyung Kim, Jae Young Jang, Yun Sung Cho, Jong Bhak, Kwang-Hyun Cho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86ee2fda1dd641cb9579c98655da26e0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:86ee2fda1dd641cb9579c98655da26e0
record_format	dspace
spelling	oai:doaj.org-article:86ee2fda1dd641cb9579c98655da26e02021-12-02T17:30:34ZIdentifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging10.1038/s41598-021-91811-12045-2322https://doaj.org/article/86ee2fda1dd641cb9579c98655da26e02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91811-1https://doaj.org/toc/2045-2322Abstract Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.Hwang-Yeol LeeYeonsu JeonYeon Kyung KimJae Young JangYun Sung ChoJong BhakKwang-Hyun ChoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hwang-Yeol Lee Yeonsu Jeon Yeon Kyung Kim Jae Young Jang Yun Sung Cho Jong Bhak Kwang-Hyun Cho Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
description	Abstract Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.
format	article
author	Hwang-Yeol Lee Yeonsu Jeon Yeon Kyung Kim Jae Young Jang Yun Sung Cho Jong Bhak Kwang-Hyun Cho
author_facet	Hwang-Yeol Lee Yeonsu Jeon Yeon Kyung Kim Jae Young Jang Yun Sung Cho Jong Bhak Kwang-Hyun Cho
author_sort	Hwang-Yeol Lee
title	Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
title_short	Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
title_full	Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
title_fullStr	Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
title_full_unstemmed	Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
title_sort	identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/86ee2fda1dd641cb9579c98655da26e0
work_keys_str_mv	AT hwangyeollee identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT yeonsujeon identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT yeonkyungkim identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT jaeyoungjang identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT yunsungcho identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT jongbhak identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging AT kwanghyuncho identifyingmoleculartargetsforreverseagingusingintegratednetworkanalysisoftranscriptomicandepigenomicchangesduringaging
_version_	1718380740075323392

Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging

Ejemplares similares