Gut Probiotic E. faecalis SI-FC-01 Extends C. elegans Lifespan via AKT/DAF-16 Pathway

Aging research seeks safe interventions to boost healthspan and lifespan. A team at University of Science and Technology of China and Hefei Institutes of Physical Science tested Enterococcus faecalis SI-FC-01, a human gut isolate, in the nematode Caenorhabditis elegans. This probiotic strain proved safe, non-hemolytic and antibiotic-susceptible, making it a strong candidate for dietary supplementation studies.

Significant Lifespan Extension

In controlled assays, L4-stage worms fed a 1:1 mix of E. faecalis SI-FC-01 and standard E. coli OP50 showed a 33.55% increase in average lifespan compared to OP50 alone (p<0.001). This matched the effect of 50 mM metformin, a known anti-aging compound, but without adverse developmental changes in body size or feeding rate.

Healthspan Improvements

• Motility: Head thrash rate improved by 26.4% at day 12.
• Learning: Enhanced salt-aversion learning index, reflecting better neural function.
• Lipofuscin: Age pigment accumulation decreased by up to 34.9% at day 12.

Gonadal cell apoptosis was also reduced, indicating preservation of reproductive tissue integrity.

Mechanism via AKT/DAF-16 Signaling

RNA-seq and qRT-PCR revealed downregulation of age-1, akt-1 and akt-2 mRNA, with daf-16 unchanged. Fluorescent imaging of TJ356 daf-16(zls356) worms showed DAF-16 translocating to nuclei in 62.2% of SI-FC-01-fed worms versus 10% in controls. Lifespan and stress-resistance benefits disappeared in daf-16, age-1, akt-1 and akt-2 mutants, confirming reliance on AKT/DAF-16 signaling.

Neuroprotection in Disease Models

Supplementing SI-FC-01 reduced polyglutamine aggregates in AM140 Huntington’s model at days 4 and 8. In BZ555 Parkinson’s model, SI-FC-01 restored dopaminergic neuron GFP fluorescence after 6-OH DA-induced damage. These findings suggest the probiotic’s stress-resistance benefits also confer neuroprotective effects.

Implications and Outlook

This study positions E. faecalis SI-FC-01 as a promising nutraceutical for delaying aging and mitigating neurodegeneration. By activating DAF-16/FOXO targets through AKT pathway modulation, it enhances antioxidant defense and immune gene expression. Future work may explore translation to mammalian systems and human trials.

Keywords: probiotic longevity, healthspan, AKT signaling, DAF-16, C. elegans models, neuroprotection.

Key points

• Enterococcus faecalis SI-FC-01 prolongs C. elegans lifespan by ~33% and boosts healthspan metrics.
• Longevity effect requires AKT/DAF-16 signaling pathway, showing DAF-16 nuclear translocation.
• SI-FC-01 reduces neurodegenerative markers in Huntington’s and Parkinson’s worm models.