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 mutation affecting sensory neurons, and the fly line was not long-lived against proper transgenic controls. Dietary restriction extended fly lifespan independently of dSir2.

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. The authors are explicit that this does not rule out a sirtuin role in mammalian lifespan — it removes the foundational invertebrate evidence the field was built on.