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Abstract: >Metabolism is intimately linked to aging. There is a growing number of studies showing that endogenous metabolites may delay aging and improve healthspan. Through the analysis of existing transcriptome data, we discover a link between activation of the transsulfuration pathway and a transcriptional program involved in peroxisome function and biogenesis in long-lived glp-1(e2141ts) mutant Caenorhabditis elegans worms. Subsequently, we show that supplementation with α-ketobutyrate, an intermediate of the transsulfuration pathway, extends lifespan in wild-type worms. Alpha-ketobutyrate augments the production of NAD+ via the lactate dehydrogenase LDH-1, leading to SIR-2.1/SIRT1-mediated enhanced peroxisome function and biogenesis, along with a concomitant increase in the expression of acox-1.2/ACOX1 in the peroxisomal fatty acid β-oxidation pathway. ACOX-1.2/ACOX1 promotes H2O2 formation, thereby resulting in activation of SKN-1/NRF2. This transcription factor in turn extends the lifespan of worms by driving expression of autophagic and lysosomal genes. Finally, we show that α-ketobutyrate also delays the cellular senescence in fibroblast cells through the SIRT1-ACOX1-H2O2-NRF2 pathway. This finding uncovers a previously unknown role for α-ketobutyrate in organismal lifespan and healthspan by coordinating the NAD+-SIRT1 signaling and peroxisomal function.

Where does one get alpha-ketobutyrate and are they by chance in pizza and cheeseburgers? Please say yes.

Get your filthy hands off my c. elegans!

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Really disappointed to read this in the science subreddit. C elegans is a very powerful model for research into multicellular organisms, which includes humans. Here's a review that I hope will change your opinion about the importance of research in roundworms.

Yes. If you skip the bun/crust…

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This is weak, try harder

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Someone please ELI5, this looks interesting

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Filing this away for my research on NHRs in Drosophila.

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In conclusion, our findings present new insights into the mechanism underlying endogenous metabolite-mediated longevity. Besides α-KB, other endogenous metabolites, such as oxaloacetate72, ω-6 polyunsaturated fatty acids73, and α-ketoglutarate74, can also delay aging and extend lifespan, suggesting that the key to longevity is hidden in our body. The endogenous metabolites provide new approaches for the prevention and treatment of aging and aging-related diseases

Scrolled for a very long time skim reading to find this.

How does one get or source alpha-ketobutyrate?

Edit: I did read about Olive oil, Mediterranean diet and also some polyphenol extracts but wasn't sure what foods specifically apart from olive oils.

Alpha-ketoglutarate is produced in the body and is not found in food. However, as studies show, fasting and exercise can increase alpha-ketoglutarate levels in the blood. Another way to absorb alpha-ketoglutarate is through dietary supplements.

Careful with supplements though. A lot of the time, your replacing something that the body makes naturally makes the body make less of it naturally and can form a dependency where you become deficient if you stop taking the supplement.

Computer says no