Life span extension by targeting a link between metabolism and histone acetylation in
            <i>Drosophila</i>

Peleg, Shahaf; Feller, Christian; Forné, Ignasi; Schiller, Evelyn; Sévin, Daniel C.; Schauer, Tamás; Regnard, Catherine; Straub, Tobias; Prestel, Matthias; Klima, Caroline; Nogueira, Melanie Schmitt; Becker, Lore; Klopstock, Thomas; Sauer, Uwe; Becker, Peter B.; Imhof, Axel; Ladurner, Andreas G.

doi:10.15252/embr.201541132

Cited by 119 publications

(162 citation statements)

References 63 publications

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“…Targeted reduction of ATP citrate lyase, an acetyl-CoA producing enzyme and the acetyltransferase for H4K12, Chameau, promotes longevity (Peleg et al, 2016). However, the exact role of acetylation in limiting lifespan in flies is still unclear.…”

Section: Nutrient Signaling and Its Effects On The Chromatinmentioning

confidence: 99%

Epigenetic Mechanisms of Longevity and Aging

Sen

Shah

Nativio

et al. 2016

Cell

723

591

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Summary Aging is an inevitable outcome of life, characterized by progressive decline in tissue and organ function and increased risk of mortality. Accumulating evidence links aging to genetic and epigenetic alterations. Given the reversible nature of epigenetic mechanisms, these pathways provide promising avenues for therapeutics against age-related decline and disease. In this review, we provide a comprehensive overview of epigenetic studies from invertebrate organisms, vertebrate models, tissue and in vitro systems. We establish links between common operative aging pathways and hallmark chromatin signatures that can be used to identify “druggable” targets to counter human aging and age-related disease.

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Section: Nutrient Signaling and Its Effects On The Chromatinmentioning

confidence: 99%

Epigenetic Mechanisms of Longevity and Aging

Sen

Shah

Nativio

et al. 2016

Cell

723

591

View full text Add to dashboard Cite

show abstract

“…This suggests that SCFAs not only simply inhibit microglia, but rather support precise tuning to ensure necessary functioning under non-inflammatory conditions. Moreover, a study in Drosophila could demonstrate that SCFAs decreased longevity through a connection between metabolism and histone acetylation (Peleg et al, 2016).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Stilling

Wouw

Clarke

et al. 2016

Neurochemistry International

633

455

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“…Fasting or caloric restriction leads to a drop of acetyl-CoA levels in heart, muscle, and liver tissue (Hebert et al 2013;Mariño et al 2014). Acetyl-CoA levels have even been shown to vary during embryonic development and aging (Tsuchiya et al 2014;Peleg et al 2016). These observations raise the question of whether changes in acetyl-CoA levels may van der Knaap and Verrijzer have an impact on chromatin acetylation and transcription.…”

Section: The Interface Between Metabolism and Gene Expressionmentioning

confidence: 99%

Undercover: gene control by metabolites and metabolic enzymes

2016

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To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awareness that central components of intermediary metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such, their concentrations constitute a potential regulatory interface between the metabolic and chromatin states. In addition, there is increasing evidence for a direct involvement of classic metabolic enzymes in gene expression control. These dual-function proteins may provide a direct link between metabolic programing and the control of gene expression. Here, we discuss our current understanding of the molecular mechanisms connecting metabolism to gene expression and their implications for development and disease.Metabolism and gene regulation are two fundamental biological processes that are essential to all living organisms. Homeostasis, cell growth, and differentiation all require the coordination of metabolic state and gene expression programs. Nevertheless, how expression of the genome adapts to metabolic state or environmental changes is not well understood. One level of regulation involves signal transduction pathways that control key transcription factors that act as master regulators of gene expression programs. In addition, post-translational modifications (PTMs) of chromatin play a major role in the activation or repression of gene transcription. These include acetylation, methylation, and phosphorylation of the histones and DNA methylation. Some of these chromatin modifications are involved in the maintenance of stable patterns of gene expression, usually referred to as epigenetic regulation. Pertinently, the activity of enzymes that modulate chromatin is critically dependent on central metabolites as cofactors or cosubstrates. Thus, the availability of metabolites that are required for the activity of histone-modifying enzymes may connect metabolism to chromatin structure and gene expression. Finally, selective metabolic enzymes act in the nucleus to adjust gene transcription in response to changes in metabolic state. Here, we review the interface between metabolism and gene transcription. We focus on the molecular mechanisms involved and discuss unresolved issues and implications for development and disease. The basics of metabolism and gene expression controlMetabolism is the total of all chemical reactions in cells and organisms that maintain life. Metabolism can be divided into two classes: catabolic processes (the breakdown of molecules that usually results in the release of energy) and anabolic processes (the synthesis of components such as proteins, lipids, and nucleic acids, which costs energy). Cellular (or intermediary) metabolism is organized in separate chemical pathways formed by a chain of linked enzymatic reactions in wh...

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Life span extension by targeting a link between metabolism and histone acetylation in Drosophila

Cited by 119 publications

References 63 publications

Epigenetic Mechanisms of Longevity and Aging

Epigenetic Mechanisms of Longevity and Aging

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Undercover: gene control by metabolites and metabolic enzymes

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