Cell Reports study combines five laboratory models to screen for compounds that extend lifespan
Cell Reports study combines five laboratory models to screen for compounds that extend lifespan
On August 31, Cell Reports published a study describing compatible experiments in yeast, worms, flies, short-lived fish, and mice. The authors automated survival measurements so that they could compare compound effects across organisms and experimental conditions.
A mouse experiment that starts treatment late in life and tests a compound known to extend lifespan in laboratory models takes between one year and a year and a half. Selecting the next compound for such an experiment requires comparable results from faster models. Dose, diet, genetic background, and monitoring methods vary among studies, so the same candidate can produce different results.
The authors developed compatible systems for five models. In yeast, a miniaturized viability assay accounts for medium acidity, which can itself affect cell survival. Cameras record worms and flies at defined intervals, and software identifies death from persistent immobility. For killifish, a short-lived fish, the authors standardized drug-containing pellets. In mice, interventions begin late in life, and the researchers monitor activity as well as lifespan.
The authors conducted a complete comparison of 423 compounds in three fast models: yeast, worms, and flies. Of these, 130 extended lifespan in at least one species, 32 did so in two species, and metformin, rifampicin, and furazolidone did so in all three.
In experiments with canagliflozin, the drug extended lifespan in male mice but had no such effect in females. When treatment began late in life, females lived shorter lives, and subsequent work linked this outcome to an approximately 20-fold higher blood concentration of the compound. The next test should therefore examine dose, sex, diet, and delivery method.
The five compatible systems can guide the selection of the next long mouse experiment. They show whether a result persists across species and conditions, and they identify where it depends on dose, sex, diet, or delivery method.