ArticleProceedings of the National Academy of Sciences of the United States of America2021
The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed.
- Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.Aging cell · 2023Trial
- Epidemiological and Metabolic Characteristics ofAnimals : an open access journal from MDPI · 2026Article
- Article
- Article
- Optimizing Body Composition During Weight Loss: The Role of Amino Acid Supplementation.Nutrients · 2025Review
- Sustained Glucose Turnover Flux Distinguishes Cancer Cachexia from Nutrient Limitation.bioRxiv : the preprint server for biology · 2025Article
- Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.GeroScience · 2024Article
- Independent and combined effects of calorie restriction and AICAR on glucose uptake and insulin signaling in skeletal muscles from 24-month-old female and male rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2024Article
- The Effects of Graded Levels of Calorie Restriction: XX. Impact of Long-Term Graded Calorie Restriction on Survival and Body Mass Dynamics in Male C57BL/6J Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- The Effects of Graded Levels of Calorie Restriction: XIX. Impact of Graded Calorie Restriction on Protein Expression in the Liver.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Profile of John R. Speakman.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the "disposable soma" and "clean cupboards" ideas. Across the four tissues, we identified more than 10,000 different metabolic features. CR altered the metabolome in a graded fashion. More restriction led to more changes. Most changes, however, were tissue specific, and in some cases, metabolites changed in opposite directions in different tissues. Only 38 common metabolic features responded to restriction in the same way across all four tissues. Fifty percent of the common altered metabolites were carboxylic acids and derivatives, as well as lipids and lipid-like molecules. The top five modulated canonical pathways were l-carnitine biosynthesis, NAD (nicotinamide adenine dinucleotide) biosynthesis from 2-amino-3-carboxymuconate semialdehyde,
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.