Universität zu Köln

Chamoli, Manish ORCID: 0000-0003-0339-7894, Goyala, Anita, Tabrez, Syed Shamsh, Siddiqui, Atif Ahmed, Singh, Anupama ORCID: 0000-0002-9311-073X, Antebi, Adam, Lithgow, Gordon J., Watts, Jennifer L. and Mukhopadhyay, Arnab ORCID: 0000-0002-5266-7849 (2020). Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction. Nat. Commun., 11 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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Abstract

The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of Xenobiotic Detoxification Program (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span. Metabolic reprogramming during Dietary Restriction (DR) activates cytoprotective gene expression. Here the authors show that PUFAs generated during DR signal via the p38-MAPK pathway to enhance cytoprotective gene expression, contributing to increased longevity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chamoli, Manish UNSPECIFIED orcid.org/0000-0003-0339-7894 UNSPECIFIED Goyala, Anita UNSPECIFIED UNSPECIFIED UNSPECIFIED Tabrez, Syed Shamsh UNSPECIFIED UNSPECIFIED UNSPECIFIED Siddiqui, Atif Ahmed UNSPECIFIED UNSPECIFIED UNSPECIFIED Singh, Anupama UNSPECIFIED orcid.org/0000-0002-9311-073X UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED Lithgow, Gordon J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Watts, Jennifer L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mukhopadhyay, Arnab UNSPECIFIED orcid.org/0000-0002-5266-7849 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-318294
DOI:	10.1038/s41467-020-18690-4
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACTIVATED PROTEIN-KINASES; ELEGANS LIFE-SPAN; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; SIGNALING PATHWAYS; OXIDATIVE STRESS; LINOLEIC-ACID; CELL-DEATH; LONGEVITY; CONTRIBUTES Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31829