NDGA

NDGA is a plant lignan from the creosote bush, and it has a rare distinction in lifespan research: its effect was replicated across three separate doses within the same programme, dose-dependently, which very few compounds manage.

It is also hepatotoxic, and that is not a theoretical concern. Chaparral, the herbal product made from the same plant, was associated with cases of serious liver injury and was the subject of regulatory action.

So the compound sits in an awkward position: a genuinely replicated male-specific lifespan effect in mice, attached to a known human liver risk, with no human ageing evidence at all.

One detail matters for interpretation. It extended median lifespan and not maximal lifespan, which is a different kind of result from 17-alpha-estradiol's. Extending median without extending maximum usually indicates reduced early mortality rather than a slowing of ageing itself.

The male-specific pattern is the most under-discussed finding in this whole field. Several of the programme's most reliable positives extend lifespan in male mice and not in female mice, and the effect is not a matter of statistical power: the female curves simply do not move. Nobody has established why. Proposed explanations include differences in drug metabolism, in baseline mortality causes between the sexes in this strain, and in hormonal context. What it means practically is that a headline reading a compound extends lifespan in mice is frequently describing an effect in half the animals, and that half is usually not stated.

NDGA also illustrates a distinction this site cares about and most coverage collapses. Median lifespan is the age by which half the animals have died; maximal lifespan is how long the longest-lived get. A compound that raises median without raising maximal has most likely removed something that was killing animals early, which is valuable and is not the same as slowing ageing. 17-alpha-estradiol raised both at its higher dose. NDGA raised only median across all three doses tested.

The Interventions Testing Program is run by the National Institute on Aging at three independent sites, using UM-HET3 mice, a genetically heterogeneous four-way cross, so a result cannot be an artefact of one inbred strain. Both sexes are tested, cohorts are large enough to detect roughly a 10 percent change in lifespan, and nulls are published alongside positives. Nothing else in ageing research has that combination, which is why its results carry more weight than a single-laboratory finding and why its failures to replicate are worth as much attention as its successes.