EXPLORING ACETYL-COA-MEDIATED BETA-HYDROXYBUTYRATE ENRICHMENT IN YEAST - A MECHANISTIC LINK TO LONGEVITY

Sep 29, 2026

Investigates β-hydroxybutyrate (βHB) as a ketone body involved in caloric restriction (CR)-mediated longevity using Saccharomyces cerevisiae. Although canonical ketogenesis enzymes are absent in yeast, βHB is detected in stationary-phase and CR conditions via metabolomics, GC-MS, and luminescence assays. Alternative carbon sources and acetoacetate supplementation increase βHB. Mitochondrial acetyl-CoA metabolism and mtFAS pathways are identified as critical drivers. βHB supplementation extends chronological lifespan dose-dependently, and CR plus βHB produces additive effects. Transcriptomics reveal shared TCA and amino-acid responses and βHB-specific mitochondrial translation and stress pathways.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Background

Caloric restriction and lifespan mechanisms

Study Design and Methods

βHB detection across conditions

Metabolomics, GC-MS, and luminescence assays

Mechanistic Findings

Enzyme-independent ketogenesis signals

Role of acetyl-CoA metabolism and mtFAS

βHB enrichment drivers

Effects on Longevity

Dose-dependent lifespan extension

Additive impact of CR + βHB

Transcriptomic Insights

Overlapping genes and βHB-exclusive targets

Shared versus βHB-specific pathways

FAQs

Why is this study focused on β-hydroxybutyrate (βHB) and caloric restriction (CR)?

CR extends lifespan across species, but its metabolic mechanisms are not fully understood. This study examines whether βHB is involved in CR-mediated longevity in yeast.

How did the researchers detect βHB in yeast despite the absence of canonical ketogenesis enzymes?

They detect βHB in stationary-phase and CR conditions using metabolomics, GC-MS, and luminescence assays, showing yeast can produce or accumulate βHB under these states.

What mechanisms and pathways were critical for βHB enrichment during CR?

The study identifies mitochondrial acetyl-CoA metabolism via ACS1 and the mtFAS pathway as critical for enriching βHB during CR.

How does βHB supplementation affect lifespan, and what does transcriptomic profiling reveal?

βHB supplementation extends chronological lifespan dose-dependently, and combining CR with βHB gives additive extension. Transcriptomics show overlapping targets related to TCA cycle and amino acid metabolism, plus βHB-exclusive targets including mitochondrial translation and stress response pathways.

Sep 29, 2026

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