Deficiency of metallothionein-1 and -2 genes shortens the lifespan of the 129/Sv mouse strain

• Metallothionein knockout mice had shorter lifespans than wild-type mice.
• Metallothionein genes are responsible for the determination of lifespan in mice.
• Enhanced senescence due to absence of metallothionein genes may shorten lifespan.

Metallothionein (MT) family proteins are small molecular weight and cysteine-rich proteins that regulate zinc homeostasis and have potential protective effects against oxidative stress and toxic metals. To investigate whether MTs play a role in longevity determination in mammals, we measured the lifespans of wild-type (WT) and MT-1 and -2 gene knockout (MTKO) mice in a 129/Sv genetic background. MTKO mice of both sexes had shorter lifespans than WT mice. In particular, male MTKO mice living beyond the mean lifespan exhibited signs of weight loss, hunchbacked spines, lackluster fur and an absence of vigor. These results suggest that lifespan is shortened due to accelerated senescence in the absence of MT genes.