Amino acid homeostasis and signalling in mammalian cells and organisms

Biochemical Journal, Journal Year: 2017, Volume and Issue: 474(12), P. 1935 - 1963

Published: May 25, 2017

Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to acid oxidation. Homeostasis achieved through exchange essential with non-essential and the transfer groups from oxidised biosynthesis. This homeostatic condition maintained an active mTORC1 complex. Under depletion, inactivated. increases breakdown cellular autophagy reduces protein The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting transcription genes involved transport biosynthesis acids. Metabolism autoregulated minimise oxidation Systemic levels are also tightly regulated. Food intake briefly plasma levels, which stimulates insulin release mTOR-dependent synthesis muscle. Excess oxidised, increased urea production. Short-term fasting does not result depletion reduced onset autophagy. Owing fact half all essential, reduction only two measures reduce demand. Long-term malnutrition causes CNS appears generate protein-specific response upon avoidance inadequate diet. High contrast, contribute together other nutrients food intake.

Language: Английский

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The quest to slow ageing through drug discovery

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(8), P. 513 - 532

Published: May 28, 2020

Language: Английский

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Commensal bacteria and essential amino acids control food choice behavior and reproduction

PLoS Biology, Journal Year: 2017, Volume and Issue: 15(4), P. e2000862 - e2000862

Published: April 25, 2017

Choosing the right nutrients to consume is essential health and wellbeing across species. However, factors that influence these decisions are poorly understood. This particularly true for dietary proteins, which important determinants of lifespan reproduction. We show in Drosophila melanogaster, amino acids (eAAs) concerted action commensal bacteria Acetobacter pomorum Lactobacilli critical modulators food choice. Using a chemically defined diet, we absence any single eAA from diet sufficient elicit specific appetites acid (AA)-rich food. Furthermore, buffer animal lack eAAs: both increased yeast appetite decreased reproduction induced by deprivation rescued presence commensals. Surprisingly, effects do not seem be due changes AA titers, suggesting gut act through different mechanism change behavior Thus, eAAs potent feeding reproductive output. demonstrates how interaction with microbiome can shape behavioral life history traits.

Language: Английский

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Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control

Nature Metabolism, Journal Year: 2019, Volume and Issue: 1(5), P. 532 - 545

Published: April 29, 2019

Language: Английский

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Horizons in the evolution of aging

BMC Biology, Journal Year: 2018, Volume and Issue: 16(1)

Published: Aug. 20, 2018

Between the 1930s and 50s, evolutionary biologists developed a successful theory of why organisms age, firmly rooted in population genetic principles. By 1980s evolution aging had secure experimental basis. Since force selection declines with evolves due to mutation accumulation or benefit fitness early life. Here we review major insights challenges that have emerged over last 35 years: does not always necessarily decline age; higher extrinsic (i.e., environmentally caused) mortality accelerate aging; conserved pathways control rate; senescence patterns are more diverse than previously thought; is universal; trade-offs involving lifespan can be 'broken'; might 'druggable'; human life expectancy continues rise but compressing late-life morbidity remains pressing challenge.

Language: Английский

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Drosophila as a model for ageing

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2017, Volume and Issue: 1864(9), P. 2707 - 2717

Published: Sept. 29, 2017

Language: Английский

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Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism

Nutrients, Journal Year: 2021, Volume and Issue: 13(8), P. 2592 - 2592

Published: July 28, 2021

Threonine (Thr), an essential amino acid for animals and the limiting in swine poultry diets, which plays a vital role modulation of nutritional metabolism, macromolecular biosynthesis, gut homeostasis. Current evidence supports that supplementation Thr leads to benefits terms energy metabolism. is not only important component gastrointestinal mucin, but also acts as modulator influences intestinal immune system via complex signaling networks, particularly mitogen-activated protein kinase (MAPK) target rapamycin (TOR) signal pathway. recognized indispensable nutrient cell growth proliferation. Hence, optimization requirement may exert favorable impact on factors linked health diseases animals. This review focuses latest reports metabolic pathways regulation, well relationship between relevant physiological functions.

Language: Английский

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The hyperfunction theory: An emerging paradigm for the biology of aging

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 74, P. 101557 - 101557

Published: Jan. 3, 2022

Language: Английский

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Gene expression hallmarks of cellular ageing

Biogerontology, Journal Year: 2018, Volume and Issue: 19(6), P. 547 - 566

Published: Feb. 28, 2018

Ageing leads to dramatic changes in the physiology of many different tissues resulting a spectrum pathology. Nonetheless, lines evidence suggest that ageing is driven by highly conserved cell intrinsic processes, and set unifying hallmarks has been defined. Here, we survey reports age-linked basal gene expression across eukaryotes from yeast human identify six cellular ageing: downregulation genes encoding mitochondrial proteins; protein synthesis machinery; dysregulation immune system genes; reduced growth factor signalling; constitutive responses stress DNA damage; mRNA processing. These encompass widely reported features such as increased senescence inflammation, electron transport chain activity ribosome synthesis, but also reveal surprising lack known stresses. We discuss how existence transcriptomic relates genome-wide epigenetic differences underlying clocks, changing transcriptome results proteomic alterations where data available variations characteristic ageing. Identification events occur during distant organisms should be informative mechanisms ageing, provide additional biomarkers assess effects diet other environmental factors on rate

Language: Английский

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Life-History Evolution and the Genetics of Fitness Components inDrosophila melanogaster

Genetics, Journal Year: 2020, Volume and Issue: 214(1), P. 3 - 48

Published: Jan. 1, 2020

Life-history traits or "fitness components"-such as age and size at maturity, fecundity fertility, age-specific rates of survival, life span-are the major phenotypic determinants Darwinian fitness. Analyzing evolution genetics these targets selection is central to our understanding adaptation. Due its simple rapid cycle, cosmopolitan distribution, ease maintenance in laboratory, well-understood evolutionary genetics, versatile genetic toolbox, "vinegar fly"

Language: Английский

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