Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila

Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD · Nature

The reported lifespan extension from sirtuin overexpression disappeared once genetic background was standardised: in worms the longevity tracked a second-site dye-filling mutation affecting sensory neurons and vanished on outcrossing, and the fly lines were longer-lived than wild type but not than the appropriate transgenic controls. Dietary restriction extended fly lifespan normally in dSir2 deletion mutants, in trials by two independent teams, so it did not require dSir2. The same study found resveratrol did not activate dSir2 deacetylase activity on a native histone H4 peptide.

Population

Caenorhabditis elegans and Drosophila melanogaster lines overexpressing sirtuins

Intervention

Outcrossing to standardise genetic background, plus appropriate transgenic controls

Comparator

Previously published sirtuin-overexpressing lines

Limitations

Invertebrates, and the paper speaks to no others. Its own qualification is narrower than the result is often given: sirtuins can still affect lifespan under particular conditions, and the authors cite a C. elegans daf-2 mutant in which deleting sir-2.1 reproducibly lengthens life. What the study removes is the foundational invertebrate evidence the field was built on.