ArticleAging2014
D-beta-hydroxybutyrate extends lifespan in C. elegans.
Article in Aging, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 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
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.
- Relationship between Aging and Ketogenic Diet: A Bibliometric Analysis (1995-2025)Endocrine, metabolic & immune disorders drug targets · 2026Pooled it
- Trial
- A Randomized Open-Label, Observational Study of the Novel Ketone Ester, Bis Octanoyl (R)-1,3-Butanediol, and Its Acute Effect on ß-Hydroxybutyrate and Glucose Concentrations in Healthy Older Adults.Journal of nutrition in gerontology and geriatricsTrial
- Metabolic shifts driven by host-microbial interactions.The FEBS journal · 2026Review
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- Butyrate extends health and lifespan in mice with mitochondrial deficiency.Nature communications · 2026Article
- Lifespan-Extending Endogenous Metabolites.Aging cell · 2026Review
- The Microbiome-Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions.Cells · 2026Review
- Changing chronomics of clock, immune and Parkinson's disease-associated genes in SCN and SN with aging in male Wistar rats: ketogenic diet intervention.Biogerontology · 2025Article
- Epigenetic Histone β-Hydroxybutyrylation Contributes to Renoprotection by β-Hydroxybutyrate in the Dahl Rat.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Beta-Hydroxybutyrate but not NMN supplementation mimics caloric restriction reducing early mortality in Daphnia.Biogerontology · 2025Article
- Article
- Article
- Unveiling the Anti-Aging Potential of 3HB: Lifespan Extension and Cellular Senescence Delay.Nutrients · 2025Article
- Chromatin and epigenetics in aging biology.Genetics · 2025Review
- Ketone body mediated histone β-hydroxybutyrylation is reno-protective.bioRxiv : the preprint server for biology · 2025Article
- β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.Cell chemical biology · 2025Article
- Article
- Histone β-hydroxybutyrylation is critical in reversal of sarcopenia.Aging cell · 2024Article
- The sweet escape: Are ketones a key player in unlocking healthy aging?The journal of nutrition, health & aging · 2024Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan ofC. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated ΒHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and βHB dehydrogenase activity induced by βHB addition, suggesting that F55E10.6 functions as an inducible βHB dehydrogenase. Furthermore, βHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-βHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways.
Indexed as
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What OpenQuestion 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 OpenQuestion graph.