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Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species

Methionine restriction (MetR) extends lifespan across different species and exerts beneficial effects on metabolic health and inflammatory responses. In contrast, certain cancer cells exhibit methionine auxotrophy that can be exploited for therapeutic treatment, as decreasing dietary methionine sele...

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Detalles Bibliográficos
Autores principales: Parkhitko, Andrey A., Jouandin, Patrick, Mohr, Stephanie E., Perrimon, Norbert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826121/
https://www.ncbi.nlm.nih.gov/pubmed/31460700
http://dx.doi.org/10.1111/acel.13034
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author Parkhitko, Andrey A.
Jouandin, Patrick
Mohr, Stephanie E.
Perrimon, Norbert
author_facet Parkhitko, Andrey A.
Jouandin, Patrick
Mohr, Stephanie E.
Perrimon, Norbert
author_sort Parkhitko, Andrey A.
collection PubMed
description Methionine restriction (MetR) extends lifespan across different species and exerts beneficial effects on metabolic health and inflammatory responses. In contrast, certain cancer cells exhibit methionine auxotrophy that can be exploited for therapeutic treatment, as decreasing dietary methionine selectively suppresses tumor growth. Thus, MetR represents an intervention that can extend lifespan with a complementary effect of delaying tumor growth. Beyond its function in protein synthesis, methionine feeds into complex metabolic pathways including the methionine cycle, the transsulfuration pathway, and polyamine biosynthesis. Manipulation of each of these branches extends lifespan; however, the interplay between MetR and these branches during regulation of lifespan is not well understood. In addition, a potential mechanism linking the activity of methionine metabolism and lifespan is regulation of production of the methyl donor S‐adenosylmethionine, which, after transferring its methyl group, is converted to S‐adenosylhomocysteine. Methylation regulates a wide range of processes, including those thought to be responsible for lifespan extension by MetR. Although the exact mechanisms of lifespan extension by MetR or methionine metabolism reprogramming are unknown, it may act via reducing the rate of translation, modifying gene expression, inducing a hormetic response, modulating autophagy, or inducing mitochondrial function, antioxidant defense, or other metabolic processes. Here, we review the mechanisms of lifespan extension by MetR and different branches of methionine metabolism in different species and the potential for exploiting the regulation of methyltransferases to delay aging.
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spelling pubmed-68261212019-12-01 Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species Parkhitko, Andrey A. Jouandin, Patrick Mohr, Stephanie E. Perrimon, Norbert Aging Cell Reviews Methionine restriction (MetR) extends lifespan across different species and exerts beneficial effects on metabolic health and inflammatory responses. In contrast, certain cancer cells exhibit methionine auxotrophy that can be exploited for therapeutic treatment, as decreasing dietary methionine selectively suppresses tumor growth. Thus, MetR represents an intervention that can extend lifespan with a complementary effect of delaying tumor growth. Beyond its function in protein synthesis, methionine feeds into complex metabolic pathways including the methionine cycle, the transsulfuration pathway, and polyamine biosynthesis. Manipulation of each of these branches extends lifespan; however, the interplay between MetR and these branches during regulation of lifespan is not well understood. In addition, a potential mechanism linking the activity of methionine metabolism and lifespan is regulation of production of the methyl donor S‐adenosylmethionine, which, after transferring its methyl group, is converted to S‐adenosylhomocysteine. Methylation regulates a wide range of processes, including those thought to be responsible for lifespan extension by MetR. Although the exact mechanisms of lifespan extension by MetR or methionine metabolism reprogramming are unknown, it may act via reducing the rate of translation, modifying gene expression, inducing a hormetic response, modulating autophagy, or inducing mitochondrial function, antioxidant defense, or other metabolic processes. Here, we review the mechanisms of lifespan extension by MetR and different branches of methionine metabolism in different species and the potential for exploiting the regulation of methyltransferases to delay aging. John Wiley and Sons Inc. 2019-08-28 2019-12 /pmc/articles/PMC6826121/ /pubmed/31460700 http://dx.doi.org/10.1111/acel.13034 Text en © 2019 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Parkhitko, Andrey A.
Jouandin, Patrick
Mohr, Stephanie E.
Perrimon, Norbert
Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title_full Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title_fullStr Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title_full_unstemmed Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title_short Methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
title_sort methionine metabolism and methyltransferases in the regulation of aging and lifespan extension across species
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826121/
https://www.ncbi.nlm.nih.gov/pubmed/31460700
http://dx.doi.org/10.1111/acel.13034
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