SG1002

The case for testing this was among the strongest in the whole programme. Hydrogen sulfide is a gaseous signalling molecule, and work across yeast, worms, flies and mice found it necessary for the lifespan and stress-resistance benefits of dietary restriction. Restricting protein or methionine raises endogenous hydrogen sulfide production, and blocking that production abolishes the benefit. If a single molecule mediated dietary restriction, this was the leading candidate.

SG1002 is an oral prodrug designed to raise circulating hydrogen sulfide, developed for heart failure.

The Interventions Testing Program tested it and found no significant lifespan increase in either sex. The coverage record notes it was tested at three different starting ages, which matters because a common defence of a null is that treatment began too late.

This is the most informative null in the batch, because the hypothesis behind it was the best. Hydrogen sulfide is not a speculative longevity mechanism; it is a molecule shown to be necessary for the lifespan effects of dietary restriction across multiple species. The obvious inference was that supplying it directly might reproduce some of those effects.

It did not, at three separate starting ages. The most likely explanation is the one this pattern usually has: a signalling molecule being required for an intervention does not mean supplying it reproduces the intervention. Dietary restriction changes hundreds of things at once, and hydrogen sulfide being a necessary link in the chain says nothing about whether it is sufficient on its own. That distinction, necessary against sufficient, accounts for a large share of failed longevity supplements.

The Interventions Testing Program is run by the National Institute on Aging at three independent sites, The Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center at San Antonio. It uses UM-HET3 mice, a genetically heterogeneous four-way cross, so a result cannot be an artefact of one inbred strain. Compounds are fed in the diet, both sexes are tested, cohorts are large enough to detect roughly a 10 percent lifespan change, and results are analysed by log-rank for median survival and by the Wang-Allison test for maximum lifespan. Its nulls are published alongside its positives. That combination of features does not exist anywhere else in ageing research, which is why a null here means considerably more than a null from a single laboratory.