A cell non-autonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism

AbstractCaloric restriction (CR) improves healthspan and lifespan of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological lifespan (CLS). We found that conditioned media collected from stationary phase CR cultures extended CLS when supplemented into non-restricted (NR) cultures, suggesting a potential cell non-autonomous mechanism of CR-induced lifespan regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in lifespan regulation.

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A cell non-autonomous mechanism of yeast chronological aging regulated by caloric restriction and one-carbon metabolism

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015402 ◽

2020 ◽

pp. jbc.RA120.015402

Author(s):

Elisa Enriquez-Hesles ◽

Daniel L. Smith ◽

Nazif Maqani ◽

Margaret B. Wierman ◽

Matthew D. Sutcliffe ◽

...

Keyword(s):

Caloric Restriction ◽

Carbon Metabolism ◽

Conditioned Media ◽

Transcriptional Responses ◽

Chronological Aging ◽

A Cell ◽

One Carbon Metabolism ◽

Strong Candidate ◽

The One ◽

Lifespan Regulation

Caloric restriction (CR) improves healthspan and lifespan of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological lifespan (CLS). We found that conditioned media collected from stationary phase CR cultures extended CLS when supplemented into non-restricted (NR) cultures, suggesting a potential cell non-autonomous mechanism of CR-induced lifespan regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in lifespan regulation.

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Duality of Tocopherol Isoforms and Novel Associations with Vitamins Involved in One-Carbon Metabolism: Results from an Elderly Sample of the LifeLines Cohort Study

Nutrients ◽

10.3390/nu12020580 ◽

2020 ◽

Vol 12 (2) ◽

pp. 580

Author(s):

Camilo G. Sotomayor ◽

Isidor Minović ◽

Manfred L. Eggersdorfer ◽

Ineke J. Riphagen ◽

Martin H. de Borst ◽

...

Keyword(s):

Vitamin E ◽

Carbon Metabolism ◽

Serum Vitamin ◽

Elderly Subjects ◽

Vitamin Supplement ◽

Total Lipids ◽

Metabolism Pathway ◽

Age Related ◽

One Carbon Metabolism ◽

The One

Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60–75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.

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Maternal vitamin D deficiency impact on LCPUFA and pregnancy outcome associated with alterations in the one carbon metabolism

Nutrition Research ◽

10.1016/j.nutres.2020.11.009 ◽

2020 ◽

Author(s):

Anindita A. Nandi ◽

Nisha S. Wadhwani ◽

Karuna N. Randhir ◽

Shweta D. Madiwale ◽

Juilee S. Deshpande ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Pregnancy Outcome ◽

Carbon Metabolism ◽

Maternal Vitamin ◽

One Carbon Metabolism ◽

The One

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Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer

Oncology ◽

10.1159/000509658 ◽

2020 ◽

Vol 98 (12) ◽

pp. 897-904

Author(s):

Sook Kyung Do ◽

Sun Ha Choi ◽

Shin Yup Lee ◽

Jin Eun Choi ◽

Hyo-Gyoung Kang ◽

...

Keyword(s):

Lung Cancer ◽

Carbon Metabolism ◽

Genetic Variants ◽

Early Stage ◽

Small Cell ◽

Survival Outcomes ◽

Small Cell Lung ◽

Metabolism Pathway ◽

One Carbon Metabolism ◽

The One

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54–0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13–4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08–1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10–3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41–1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11–6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17–2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12–6.88, p = 0.03, respectively). Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.

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