The broccoli derivative sulforaphane extends lifespan by slowing the transcriptional aging clock

Sulforaphane (SFN), an organosulfur isothiocyanate derived from cruciferous vegetables, has been shown to inhibit inflammation, oxidative stress, and cancer cell growth; it has also been shown to increase the lifespan of the C. elegans nematode strain N2. Here, we tested the lifespan effects of SFN following the standard experimental procedures of the Caenorhabditis Intervention Testing Program (CITP). The CITP, a multi-institute research consortium, aims to identify chemical interventions that can robustly and reproducibly promote health and lifespan. To investigate the functional targets of SFN, we employed bulk RNA-Seq at a variety of ages to create a “transcriptional aging clock” using control individuals and then tested how global patterns of gene expression are altered under SFN treatment. Multi-dimensional scaling analysis of the transcriptome revealed transcriptional age under SFN treatment was similar to control individuals approximately four days younger, representing a nearly 20% shift relative to overall lifespan. These results support the idea that robust longevity-extending interventions can act via global effects across the organism, as revealed at a functional level via changes in gene expression. We performed differential gene expression analysis comparing SFN-treated and DMSO control samples in 2, 4, 8, 12, and 16-day old adult worms in the wildtype N2 strain.