New Aspects in Metabolism of Aging

Abstract In recent years there has been a renewed emphasis on metabolism as a key contributor to a host of chronic non-communicable conditions: cancer, neurodegeneration, frailty, and functional declines in immune and inflammatory processes. All share a common connection in metabolic dysfunction. Furthermore, aging itself is associated with changes in metabolism, although the underlying drivers for these changes are unknown. Here we introduce speakers working at the cutting edge in metabolism research, and whose studies are of direct relevance to aging. Dr. Chandel will focus on mitochondrial biology, describing recent advances in understanding the mechanisms of the beneficial effects of metformin. Dr. Haigis takes the mitochondrial theme to cancer biology, the area of research that revived metabolic perspectives in biomedical research. Dr. Najt’s talk describes a less well studied organelle, the lipid droplet, and its role in a rapidly expanding area of research on lipid metabolic regulation specifically in the context of aging. Dr. Brown-Borg will present data on nutritional and genetic modulation of metabolism and how pathways converge to influence chromatin and epigenetic regulation of gene expression. Together our speakers explore new concepts in metabolism research that are of particular relevance to aging. This session aligns with the concept of GeroScience, the more we know of aging biology the better we understand diseases and disorders of aging. This session will demonstrate that metabolism, its regulation, and its influence on key processes linked to health and longevity, place it in a central position as we seek to discover targets and interventions to improve human aging.

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Metabolic regulation of gene expression through histone acylations

Nature Reviews Molecular Cell Biology ◽

10.1038/nrm.2016.140 ◽

2016 ◽

Vol 18 (2) ◽

pp. 90-101 ◽

Cited By ~ 270

Author(s):

Benjamin R. Sabari ◽

Di Zhang ◽

C. David Allis ◽

Yingming Zhao

Keyword(s):

Gene Expression ◽

Metabolic Regulation ◽

Regulation Of Gene Expression

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Many Routes from Glycolysis to Histone PTMs. Nature “Matters Arising” response to: Zhang et al. Metabolic regulation of gene expression by histone lactylation. (2019) Nature. 574(7779), 575-580.

10.31219/osf.io/sba8j ◽

2020 ◽

Author(s):

Chaitanya A. Kulkarni ◽

Paul Brookes

Keyword(s):

Gene Expression ◽

Small Molecule ◽

Metabolic Regulation ◽

Regulation Of Gene Expression ◽

Histone Mark ◽

Acetyl Coa ◽

Post Translational Modifications ◽

Histone Ptms

Multiple histone post-translational modifications (PTMs) originate from small molecule metabolites (e.g. acetyl-lysine from acetyl-CoA) 1. As such, we read with interest the recent Nature paper from Zhang et al. 2 reporting discovery of lysine lactylation as a novel histone mark originating from the metabolite lactate. However, several concerns arise regarding the identity and source of this novel PTM.

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Faculty Opinions recommendation of Metabolic regulation of gene expression by histone lactylation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736798401.793567478 ◽

2019 ◽

Author(s):

Aurelio Teleman ◽

Gianluca Figlia

Keyword(s):

Gene Expression ◽

Metabolic Regulation ◽

Regulation Of Gene Expression

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Post-transcriptional regulation of gene expression by alternative 5′-untranslated regions in carcinogenesis

Biochemical Society Transactions ◽

10.1042/bst0360708 ◽

2008 ◽

Vol 36 (4) ◽

pp. 708-711 ◽

Cited By ~ 24

Author(s):

Laura Smith

Keyword(s):

Gene Expression ◽

Transcriptional Regulation ◽

Cancer Biology ◽

Regulation Of Gene Expression ◽

Untranslated Regions ◽

Specific Distribution ◽

Eukaryotic Gene ◽

Multiple Alternative ◽

Post Transcriptional Regulation ◽

Inappropriate Expression

Post-transcriptional regulation, via 5′-UTRs (5′-untranslated regions), plays an important role in the control of eukaryotic gene expression. Recent analyses of the mammalian transcriptome suggest that most of the genes express multiple alternative 5′-UTRs and inappropriate expression of these regions has been shown to contribute to the development of carcinogenesis. The present review will focus on the complex post-transcriptional regulation of ERβ (oestrogen receptor β) expression. In particular, results from our laboratory suggest that the expression of alternative 5′-UTRs plays a key role in determining the level of ERβ protein expression. We have also shown that these alternative ERβ 5′-UTRs have a tissue-specific distribution and are differentially expressed between various normal and tumour tissues. Our results also suggest that alternative 5′-UTRs can influence downstream splicing events, thereby perhaps affecting ERβ function. These results suggest that alternative 5′-UTRs may have an overall influence on ER activity and this may have important implications for our understanding of cancer biology and treatment.

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MKL1 is a key biomarker correlated with immune infiltrates and chemosensitivity in breast cancer

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2021.6306 ◽

2021 ◽

Author(s):

Yijia Hua ◽

Mengzhu Yang

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Immune Cells ◽

Cancer Biology ◽

Drug Sensitivity ◽

Regulation Of Gene Expression ◽

Sensitivity Analyses ◽

Breast Cancer Dataset ◽

Potential Biomarker ◽

Low Expression

Megakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas (TCGA) breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer (NK) cells, macrophages, neutrophils and dendritic cells (DCs). The chromatin modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer.

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PSXII-3 Identification of key metabolic mediators during dietary tryptophan supplementation in low-birth-weight pigs by RNA sequencing

Journal of Animal Science ◽

10.1093/jas/skab235.466 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 255-255

Author(s):

Ping Xiao ◽

Parniyan Goodarzi ◽

Mohammad Habibi ◽

Kennedy Roberts ◽

Julia Sutton ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Birth Weight ◽

Low Birth Weight ◽

Rna Sequencing ◽

Metabolic Regulation ◽

Pearson Correlation ◽

Regulation Of Gene Expression ◽

Essential Amino Acids ◽

Porcine Liver

Abstract Low birth weight (LBW) is associated with the development of metabolic syndrome, diabetes mellitus and insulin resistance. While tryptophan (Trp), one of essential amino acids supplied by diet, plays an essential role in fetal growth and development, the effects of Trp supplementation on metabolic processes of postnatal LBW individuals remain unclear. The objective of this study was to identify differentially expressed (DE) genes and altered biological processes in liver of LBW and normal birth weight (NBW) piglets supplemented with Trp. RNA was isolated from liver tissues of three weeks old piglets supplemented with Trp (NBW-0% and LBW-0, 0.4, and 0.8%) and was used for RNA sequencing (RNAseq). There were 100, 191 and 39 DE genes in NBW (N0) and LBW tryptophan 0.4%, 0.8% (L4 and L8) when compared to LBW without Trp supplementation (L0). To determine whether Trp supplementation can resume metabolic regulation-related gene expression to N0 level, DE genes from N0 vs. L0 were clustered into 3 groups based on co-expression trends and clusters were enriched for genes associated with lipid catabolic process, circadian regulation of gene expression and fatty acid response. Further, eight hub genes (PID1, PAFAH2, MAP3K15, ANKRD44, CYP2J34, N4BP2L1, RUSC1 and SALL1) identified in co-expression networks based on Pearson correlation coefficient had strong co-expression coefficients (|r| > 0.9) with each other. In particular, PID1 was significantly associated with many neurological, metabolic, environmental and cardiovascular traits based on phenome-wide association analysis (Phe-WAS). In summary, our study provides novel insights into the molecular mechanism underlying LBW metabolic changes with Trp supplementation in porcine liver tissue and highlights that LBW metabolism restoration may be regulated by genes participating in fatty acid response and cardiovascular diseases.

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Metabolic regulation of chromatin modifications and gene expression

The Journal of Cell Biology ◽

10.1083/jcb.201803061 ◽

2018 ◽

Vol 217 (7) ◽

pp. 2247-2259 ◽

Cited By ~ 63

Author(s):

Juan Manuel Schvartzman ◽

Craig B. Thompson ◽

Lydia W.S. Finley

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Metabolic Regulation ◽

Regulation Of Gene Expression ◽

Enzymatic Reaction ◽

Chromatin Modifications ◽

Dynamic Regulation ◽

Local Conditions ◽

Control Of Gene Expression ◽

Cell Fate Decisions

Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.

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