ArticleAging2017
The effects of graded levels of calorie restriction: XI. Evaluation of the main hypotheses underpinning the life extension effects of CR using the hepatic transcriptome.
Article in Aging, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction.PLoS biology · 2026Article
- A functionally integrated cross-tissue alternative splicing program during short-term calorie restriction.Life metabolism · 2026Article
- Changes in the brain [NADFrontiers in aging neuroscience · 2026Review
- Article
- Review
- Hepatic metabolic reprogramming in male mice during short-term caloric restriction involves enhanced glucocorticoid rhythms.Nature communications · 2025Article
- Liver, ageing and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Article
- Maternal α-casein deficiency extends the lifespan of offspring and programmes their body composition.GeroScience · 2025Article
- Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?Antioxidants (Basel, Switzerland) · 2025Review
- Does diet influence aging? Evidence from animal studies.Journal of internal medicine · 2024Review
- SIRT7: the seventh key to unlocking the mystery of aging.Physiological reviews · 2024Review
- 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
- Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals.Cell metabolism · 2023Article
- Effects of dietary macronutrients on the hepatic transcriptome and serum metabolome in mice.Aging cell · 2022Article
- Machine learning-based predictions of dietary restriction associations across ageing-related genes.BMC bioinformatics · 2022Article
- Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice.Nature metabolism · 2021Article
- The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan. However, the expression levels of SIRT4 and SIRT7 were decreased with increasing levels of CR. Changes consistent with altered fuel utilization under CR may reduce reactive oxygen species production, which was paralleled by reduced protection. Downregulated major urinary protein (MUP) transcription suggested reduced reproductive investment. Graded CR had a positive effect on autophagy and xenobiotic metabolism, and was protective with respect to cancer signaling. CR had no significant effect on fibroblast growth factor-21 (FGF21) transcription but affected transcription in the hydrogen sulfide production pathway. Responses to CR were consistent with several different hypotheses, and the benefits of CR on lifespan likely reflect the combined impact on multiple aging related processes.
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What Socratic holds
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.