Ketone body b-Hydroxybutyrate does not extend lifespan, but upregulates fecundity in food-limited Daphnia, with a transgenerational effect

C. Pearson, A. C.; Bharda, S. C.; Yampolsky, L. Y.

doi:10.1101/2025.01.18.633735

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bioRxiv · 10.1101/2025.01.18.633735

Ketone body b-Hydroxybutyrate does not extend lifespan, but upregulates fecundity in food-limited Daphnia, with a transgenerational effect

C. Pearson, A. C.·Bharda, S. C.·Yampolsky, L. Y.

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Abstract

Ketone bodies accumulate on ketogenic diets and are known to have numerous beneficial health and longevity effects. Here we investigate the effects of exposure to environmental b-hydroxybutyrate (BHB), a ketone body, on longevity and fecundity of a model organism Daphnia magna, a plankton crustacean, maintained at limited food availability. We report that exposure to continuous or intermittent lifetime exposure to 2.5 - 10 mM of BHB reduces Daphnia lifespan, while intermittent exposure administered for 20-day periods has little effect on post-exposure survival, regardless of the age at exposure onset. On the other hand, various BHB exposure regimes significantly increased fecundity, including fecundity up to 100 days past a 20-day exposure. We further demonstrate that even relatively brief early life maternal exposure to BHB can increase daughters fecundity, although this transgenerational effect is genotype-specific. We argue that this effect must have a signaling nature rather than simply manifestation of additional source of energy provided by BHB and discuss potential significance of genetic variation in transmission of such signals.

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C. Pearson, A. C., Bharda, S. C., Yampolsky, L. Y.. 2025-01-22. Ketone body b-Hydroxybutyrate does not extend lifespan, but upregulates fecundity in food-limited Daphnia, with a transgenerational effect. https://doi.org/10.1101/2025.01.18.633735

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