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bioRxiv · 10.64898/2026.06.23.734065

Curcumin and Sulforaphane Preserve Mobility in Aging Caenorhabditis elegans via Distinct yet Complementary Transcriptional Signatures

Vivek-Ananth, R.·Sellegounder, D.·Mohanraj, K.·Maitra, S.·Saunter, C.·Weinkove, D.·Verdin, E.·Phipps, S.·Price, N.
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Abstract

Aging involves a progressive decline in bodily functions, underscoring the need for interventions that enhance healthspan. In this study, we screened nine natural products in Caenorhabditis elegans using whole-organism phenotyping to assess mobility endpoints, and subsequently focused on curcumin, sulforaphane, and their combination. In replicated follow-up experiments, all three interventions improved late-adult mobility after Day 2 of adulthood. Sulforaphane and the combination provided the strongest gains, whereas curcumin showed a distinct benefit profile, with more pronounced effects on time active measures than on speed-based metrics. To examine associated molecular changes, we performed transcriptomic profiling on Day 3 adults. Curcumin was associated with lipid and sphingolipid remodeling together with reduced expression of several innate immune effectors, whereas sulforaphane induced glutathione-linked detoxification signatures involving multiple gst genes. The combination retained major features of both single-compound responses while adding combination-specific changes that broadened detoxification-associated signatures and extended repression of lectin-and lysozyme-associated genes. Transcription factor activity inference further supported SKN-1-linked detoxification responses under sulforaphane and the combination. Overall, these results suggest that curcumin and sulforaphane engage distinct yet partially convergent maintenance-related programs, and that their combination broadens the underlying molecular response without producing additive mobility gains. These findings motivate further testing of natural product combinations in healthspan-related contexts.

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Vivek-Ananth, R., Sellegounder, D., Mohanraj, K., Maitra, S., Saunter, C., Weinkove, D., Verdin, E., Phipps, S., Price, N.. 2026-06-25. Curcumin and Sulforaphane Preserve Mobility in Aging Caenorhabditis elegans via Distinct yet Complementary Transcriptional Signatures. https://doi.org/10.64898/2026.06.23.734065

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