Very little work takes place on combinations of interventions known to target mechanisms of aging. This is largely, I suspect, for reasons relating to intellectual property and control of later development. The work that does take place usually looks at approaches known or likely to have minimal effects in long-lived species such as our own, even while producing sizable gains in short-lived species, and this open access paper follows that trend.
It is unfortunate that short-lived species exhibit a pace of aging that is so much more reactive to the environment than that of long-lived species, as it has biased a great deal of research into directions, such as analysis of the beneficial response to calorie restriction, that cannot possibly greatly extend human life span. Nonetheless, researchers presently know next to nothing about how different approaches to slowing aging interact with one another. Can ten or twenty different marginal approaches be combined to form a more impressive outcome? No-one knows, but projects such as this one may help to set expectations.
In this study, we investigated whether the combined application of several interventions with potential anti-aging action causes a cumulative effect on lifespan extension in flies. As for anti-aging drugs, we used rapamycin, the well-known mTOR signaling inhibitor, and two plant-derived compounds, particularly, alkaloid berberine and carotenoid fucoxanthin, whose geroprotective properties have been studied on different biological models.
We studied the effects of dietary restriction and co-administration of berberine, fucoxanthin, and rapamycin in constant darkness and low-temperature conditions using the D. melanogaster model. In addition, to address whether the long-lived strain demonstrates an enhanced geroprotective effect of the interventions' combinations, we studied the long-lived Enhancer of zeste (E(z)) mutant flies.
In the current study, using a combination of several geroprotective interventions, we managed to more than double the lifespan of flies, which is significantly more than using each intervention separately. This is the first report on the increase of maximum flies' lifespan to more than 200 days (120% increase). This result is most likely associated with the synergistic effect of interventions that led to a global metabolic network reorganization and ultimately to beneficially affected lifespan through the modulation of several molecular signaling pathways at once.