I don’t care too much about results in crickets in terms of indicating translation of results to humans (we don’t have much data to suggest that crickets are a specifically good model for successful translation of a small molecule to effectiveness in humans), but its good to see yet another model organism that rapamycin has proven successful in. Rapamycin has proven successful in extending lifespan in every organism its been tested in, from yeast, to fungi, to rotifers, to nematodes (worms), to fruit flies, to fish, to crustaceans, to mice and monkeys… and now crickets! The mTOR pathway has been conserved well over a billion years of evolution.
In a new study attempting to establish the house cricket (Acheta domesticus) as a scalable longevity model, researchers from the University of Washington tested intermittent “pulse” dosing of three top-tier geroprotective candidates: Rapamycin, Acarbose, and Phenylbutyrate. The results provide a stark warning against assuming “safe” diabetes drugs are universally beneficial across sexes.
While Rapamycin solidified its status as the “gold standard,” extending survival by nearly 60% in males and preserving juvenile-like cognitive and locomotor function, Acarbose—a drug widely considered benign in the biohacker community—dramatically reduced the lifespan of female crickets (Hazard Ratio ~3.0), effectively tripling their risk of death despite inducing weight gain. This contradicts established mouse data where Acarbose is sex-neutral or weakly beneficial in females, highlighting a potential metabolic “mismatch” or toxicity that could be relevant to specific human phenotypes.
Phenylbutyrate, often touted for its HDAC inhibition and ammonia scavenging, failed to extend lifespan significantly in the overall cohort but did show sex-specific survival benefits in females, albeit with reduced locomotor performance. This study reinforces the “Rapamycin or bust” trend in recent longevity literature while casting a shadow of uncertainty over Acarbose for females.
Source:
- Open Access Paper: The gerotherapeutic drugs rapamycin, acarbose, and phenylbutyrate extend lifespan and enhance healthy aging in house crickets
- Context: University of Washington School of Medicine | Journal: Research Square (Preprint)
- Impact Evaluation: The impact score of this journal is [Unrated/Preprint]
Novelty
- Durability of “Pulse” Dosing: Most longevity studies use continuous dosing. This proves that a short, 2-week “vacation” on Rapamycin in mid-life can permanently alter the survival trajectory in an invertebrate model.
- Invertebrate Validation: Establishes the cricket as a fast, cheap screening tool that (mostly) aligns with mouse data—except for the specific Acarbose/Female divergence.
Critical Limitations
- Translational Gap (Phylogeny): Crickets are insects. They lack a closed circulatory system, a liver, and a mammalian immune system. The Acarbose toxicity could be due to insect-specific carbohydrate biology that does not apply to humans.
- Small Sample Size: N=20 is statistically fragile. A few accidental deaths could skew the Hazard Ratios significantly.
- Preprint Status: The data has not been stress-tested by peer review. The “weight gain” in Acarbose females needs histological verification to ensure it wasn’t edema or egg retention/impaction rather than “healthy fat.”