Membrane fatty acid composition in Ames dwarf mice

Small mammals such as mice possess tissues containing more polyunsaturated fatty acids (PUFAs) while living shorter lives. These relationships have been combined in the `membrane pacemaker hypothesis of aging`, a recent extension of the widely accepted `oxidative stress` hypothesis of aging. We propose to test this hypothesis in the Ames dwarf mouse, a small and particularly long-living mouse model which is deficient in growth hormone, prolactin and thyroid stimulating hormone. According to the `membrane pacemaker hypothesis of aging`, Ames dwarf mice might have membranes low in PUFAs and especially low in the n-3 PUFA class, thereby facing lower lipid peroxidation and less oxidative damage. The proposed study aims to test whether membrane composition of the long-living `Ames dwarf mouse` commensurates with its body size (i.e. rich in polyunsaturated fatty acids and therefore peroxidation prone) or, alternatively, if it has a low degree of tissue polyunsaturation and thus peroxidation resistant membranes, more in keeping with its long lifespan. Along with testing a powerful mechanistic hypothesis of aging our study might emphasise the importance of membrane composition as a determinant of lifespan.

Small mammals such as mice possess tissues containing more polyunsaturated fatty acids (PUFAs) while living shorter lives. These relationships have been combined in the "membrane pacemaker hypothesis of aging", a recent extension of the widely accepted "oxidative stress" hypothesis of aging. We propose to test this hypothesis in the Ames dwarf mouse, a small and particularly long-living mouse model which is deficient in growth hormone, prolactin and thyroid stimulating hormone. According to the "membrane pacemaker hypothesis of aging", Ames dwarf mice might have membranes low in PUFAs and especially low in the n-3 PUFA class, thereby facing lower lipid peroxidation and less oxidative damage. The proposed study aims to test whether membrane composition of the long-living "Ames dwarf mouse" commensurates with its body size (i.e. rich in polyunsaturated fatty acids and therefore peroxidation prone) or, alternatively, if it has a low degree of tissue polyunsaturation and thus peroxidation resistant membranes, more in keeping with its long lifespan. Along with testing a powerful mechanistic hypothesis of aging our study might emphasise the importance of membrane composition as a determinant of lifespan.