Old Mice Hard to Replicate

Credit: © Aleksandr Lukin" /> Credit: © Aleksandr Lukin The paper: S.E. Schriner et al., "Extension of murine lifespan by overexpression of catalase targeted to mitochondria." Science, 308:1909-11, 2005. (Cited in 107 papers) The finding: Peter Rabinovitch at the University of Washington at Seattle and his colleagues found that transgenic mice overexpressing the antioxidant enzyme catalase in their mitochondria lived nearly 20% longer and exhibi

Charles Q. Choi
Feb 28, 2007
<figcaption> Credit: © Aleksandr Lukin</figcaption>
Credit: © Aleksandr Lukin

The paper:

S.E. Schriner et al., "Extension of murine lifespan by overexpression of catalase targeted to mitochondria." Science, 308:1909-11, 2005. (Cited in 107 papers)

The finding:

Peter Rabinovitch at the University of Washington at Seattle and his colleagues found that transgenic mice overexpressing the antioxidant enzyme catalase in their mitochondria lived nearly 20% longer and exhibited less heart disease and other age-related declines. This supported the free-radical theory of aging.

The problem:

Replicating the findings has proven difficult. Rabinovitch says that changes in veterinary care have led to euthanasia of mice that develop dermatitis and other ailments at early ages. This practice has confounded the replication of past longevity observations.

The verdict:

Richard Miller at the University of Michigan, Ann Arbor, offers his opinion: "If mito-Cat mutations do increase lifespan in mice, the effect may depend in complicated ways on a specific and not well-characterized set of background genes and environmental factors."

The work ahead:

Rabinovitch says he's about two-thirds of the way through aging studies with two different mouse strains. New data, he says, clarify the protection against age-related cardiac changes and nonhematologic cancers, and they are working on new transgenic models.

The 2005 data:

Mice overexpressing Mice (wt littermates) % Increase lifespan (p value)
Peroxisomal catalase #1 8 (71) 10% (not significant)
Peroxisomal catalase #2 36 (22) 13% (0.02)
Peroxisomal catalase #3 54 (73) 11% (0.003)
Nuclear targeted catalase #1 36 (46) 4% (not significant)
Nuclear targeted catalase #2 42 (52) 3% (not significant)
Mito. targeted catalase #1 42 (58) 17% (0.0001)
Mito. targeted catalase #2 20 (44) 21% (0.0002)