Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan

Correia‐Melo, Clara; Kamrad, Stephan; Tengölics, Roland; Messner, Christoph B.; Trébulle, Pauline; Townsend, StJohn; Varma, Sreejith Jayasree; Freiwald, Anja; Heineike, Benjamin M.; Campbell, Kate; Herrera-Dominguez, Lucía; Aulakh, Simran Kaur; Szyrwiel, Łukasz; Yu, Jigui; Zelezniak, Aleksej; Demichev, Vadim; Mülleder, Michael; Papp, Balázs; Alam, Mohammad Tauqeer; Ralser, Markus

doi:10.1016/j.cell.2022.12.007

Cited by 22 publications

(18 citation statements)

References 104 publications

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“…Why then has polymerization been selected by evolution? In the wild, yeast cells do not grow in test tubes but in colonies formed by interactive communities where cells may engage in crossgenerational amino acid exchange between young and aged cells 68 . Thus, Glt1 polymerization could be an example of antagonistic pleiotropy that has evolved for the benefit of the community, but at the cost of aging of the individual cell.…”

Section: Discussionmentioning

confidence: 99%

Global analysis of aging-related protein structural changes uncovers enzyme polymerization-based control of longevity

Paukštytė

Cabezas

Feng

et al. 2023

Preprint

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Aging is associated with progressive phenotypic changes over time. Virtually all cellular phenotypes are produced by proteins and structural alterations in proteins can lead to age-related diseases. Nonetheless, comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contribution to age-related phenotypes is lacking. Here, we conducted proteome-wide analysis of early age-related protein structural changes in budding yeast using limited proteolysis-mass spectrometry. The results, compiled in online ProtAge-catalog, unravelled age-related functional changes in regulators of translation, protein folding and amino acid metabolism. Mechanistically, we found that folded glutamate synthase Glt1 polymerizes into supramolecular self-assemblies during aging causing breakdown of cellular amino acid homeostasis. Inhibiting Glt1 polymerization by mutating the polymerization interface restored amino acid levels in aged cells, attenuated mitochondrial dysfunction and led to life span extension. Altogether, this comprehensive map of protein structural changes enables identifying novel mechanisms of age-related phenotypes and offers opportunities for their reversal.

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Section: Discussionmentioning

confidence: 99%

Global analysis of aging-related protein structural changes uncovers enzyme polymerization-based control of longevity

Paukštytė

Cabezas

Feng

et al. 2023

Preprint

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“…Aging has been characterized with a number of hallmarks, among which quite a few roots from abnormal metabolic activities (López-Otín et al, 2023). For example, while nutrient-sensing and mitochondrial function are primarily an intrinsic part of cell metabolism, others have a more complicated and close relationship with cellular metabolism, such as the cause of DNA damage by the imbalance of redox metabolism, alteration of mTORC activity (a conserved signaling pathway in aging) with amino acids and glucose (Liu and Sabatini, 2020), and most recently, creation of aging intervention environment through cell-cell metabolite exchange (Correia-Melo et al, 2023).…”

Section: Metabolic Dysregulationmentioning

confidence: 99%

Biomarkers of aging

Bao

Cao

Chen

et al. 2023

Sci. China Life Sci.

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Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant. Supporting Information The supporting information is available online at 10.1007/s11427-023-2305-0. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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“…The gene encoding glycerol dehydrogenase ( GAAD ) for glycerol synthesis was also upregulated by 1.03 times, which may be due to the fact that R. toruloides Z11 produces glycerol as a protective agent for cells under excessive light exposure . In addition, the gene encoding succinate dehydrogenase ( SDHB ) in the tricarboxylic acid cycle (TCA) cycle was upregulated by 1.22 times, which can improve FADH 2 production for microbial growth and carotenoid production.…”

Section: Results and Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals the Potential Mechanisms for Improving Carotenoid Production in Rhodosporidium toruloides Z11 under Light Stress

Gao,

Tang,

et al. 2024

J. Agric. Food Chem.

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Carotenoids, as a type of tetraterpene compound, have been widely used in food, medical, and health areas owing to their antioxidant, immune enhancement, and disease risk reduction effects. Rhodosporidium toruloides is a promising oleaginous red yeast that can industrially synthesize carotenoids. In this study, the effects of different light exposure times and intervals on carotenoid production by R. toruloides Z11 were first investigated. Results showed that a higher carotenoid content (1.29 mg/g) can be achieved when R. toruloides Z11 was exposed to light for 12 h per day, which was increased by 1.98 times compared with that of dark cultivation. Transcriptome profiling revealed that light stress could effectively promote the gene expression levels of GGPS1 and AL1 in the carotenoid biosynthesis pathway and phr in the DNA photolysis pathway of R. toruloides. This work will provide a molecular foundation to further improve the production efficiency of carotenoids by genetic engineering.

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Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan

Cited by 22 publications

References 104 publications

Global analysis of aging-related protein structural changes uncovers enzyme polymerization-based control of longevity

Global analysis of aging-related protein structural changes uncovers enzyme polymerization-based control of longevity

Biomarkers of aging

Transcriptomic Analysis Reveals the Potential Mechanisms for Improving Carotenoid Production in Rhodosporidium toruloides Z11 under Light Stress

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