The broccoli derivative sulforaphane extends lifespan by slowing the transcriptional aging clock
4 affiliations
- 1Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon, United States of America
- 2Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America
- 3Buck Institute for Research on Aging, Novato, California, United States of America
- 4Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America
Abstract
Sulforaphane, an organosulfur isothiocyanate derived from cruciferous vegetables, has been shown to inhibit inflammation, oxidative stress, and cancer cell growth. To explore the potential of sulforaphane as a candidate natural compound for promoting longevity more generally, we tested the dose and age-specific effects of sulforaphane on C. elegans longevity, finding that it can extend lifespan by more than 50% at the most efficacious doses, but that treatment must be initiated early in life to be effective. We then created a novel, gene-specific transcriptional aging clock, which demonstrated that sulforaphane-treated individuals exhibited a “transcriptional age” that was approximately four days younger than age-matched controls, representing a nearly 20% reduction in biological age. The clearest transcriptional responses were detoxification pathways, which, together with the shape of the dose-response curve, indicates a likely hormetic response to sulforaphane, which we show are regulated by both the daf-16/FOXO and skn-1/Nrf2 transcription factors. These results support the idea that robust longevity-extending interventions can act via global effects across the organism, as revealed by systems level changes in gene expression. Author summary: Broccoli and related vegetables contain a natural compound called sulforaphane that has been linked to several health benefits, including protection against inflammation and some cancers. We wanted to know whether it might also slow aging itself. Using the roundworm Caenorhabditis elegans, a short-lived animal widely used to study aging, we found that sulforaphane extended lifespan by more than 50%, but only at moderate doses, and only when treatment began early in adult life. At the highest dose, the benefit disappeared, a pattern suggesting that sulforaphane works as a mild stress that prompts the body to strengthen its own defenses. To measure how “old” treated worms were on the inside, we built a new aging clock based on genes whose activity changes predictably with age. By this measure, treated worms were biologically about 20% younger than untreated worms of the same age. The genes most strongly switched on were those the body uses to clear out harmful substances, and two well-known master regulators of stress responses were each partly needed for the benefit. Our work suggests that gently activating the body’s own protective systems can promote longer life and offers a new way to test other candidate anti-aging compounds.
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BibTeX
@article{sedore2026broccoli,
title = {{The broccoli derivative sulforaphane extends lifespan by slowing the transcriptional aging clock}},
author = {Christine A. Sedore and Erik Segerdell and Anna L. Coleman-Hulbert and Erik Johnson and Jonathan N. Levi and Gordon J. Lithgow and Monica Driscoll and Patrick C. Phillips},
journal = {PLOS Aging and Health},
year = {2026},
month = oct,
doi = {10.1371/journal.page.0000047},
url = {https://doi.org/10.1371/journal.page.0000047},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The broccoli derivative sulforaphane extends lifespan by slowing the transcriptional aging clock
AU - Christine A. Sedore
AU - Erik Segerdell
AU - Anna L. Coleman-Hulbert
AU - Erik Johnson
AU - Jonathan N. Levi
AU - Gordon J. Lithgow
AU - Monica Driscoll
AU - Patrick C. Phillips
PY - 2026
DA - 2026/10/27
JO - PLOS Aging and Health
DO - 10.1371/journal.page.0000047
UR - https://doi.org/10.1371/journal.page.0000047
AB - Sulforaphane, an organosulfur isothiocyanate derived from cruciferous vegetables, has been shown to inhibit inflammation, oxidative stress, and cancer cell growth. To explore the potential of sulforaphane as a candidate natural compound for promoting longevity more generally, we tested the dose and age-specific effects of sulforaphane on C. elegans longevity, finding that it can extend lifespan by more than 50% at the most efficacious doses, but that treatment must be initiated early in life to be effective. We then created a novel, gene-specific transcriptional aging clock, which demonstrated that sulforaphane-treated individuals exhibited a “transcriptional age” that was approximately four days younger than age-matched controls, representing a nearly 20% reduction in biological age. The clearest transcriptional responses were detoxification pathways, which, together with the shape of the dose-response curve, indicates a likely hormetic response to sulforaphane, which we show are regulated by both the daf-16/FOXO and skn-1/Nrf2 transcription factors. These results support the idea that robust longevity-extending interventions can act via global effects across the organism, as revealed by systems level changes in gene expression. Author summary: Broccoli and related vegetables contain a natural compound called sulforaphane that has been linked to several health benefits, including protection against inflammation and some cancers. We wanted to know whether it might also slow aging itself. Using the roundworm Caenorhabditis elegans, a short-lived animal widely used to study aging, we found that sulforaphane extended lifespan by more than 50%, but only at moderate doses, and only when treatment began early in adult life. At the highest dose, the benefit disappeared, a pattern suggesting that sulforaphane works as a mild stress that prompts the body to strengthen its own defenses. To measure how “old” treated worms were on the inside, we built a new aging clock based on genes whose activity changes predictably with age. By this measure, treated worms were biologically about 20% younger than untreated worms of the same age. The genes most strongly switched on were those the body uses to clear out harmful substances, and two well-known master regulators of stress responses were each partly needed for the benefit. Our work suggests that gently activating the body’s own protective systems can promote longer life and offers a new way to test other candidate anti-aging compounds.
SN - 3070-801X
ER -